INBRIJA

Anti-Parkinson Agents, Dopamine Precursors

Oral inhalation powder (capsules for oral inhalation; i.e., Inbrija)
Each carton contains capsules in foil blister strips and 1 inhaler.
The capsules are for oral inhalation using the manufacturer supplied inhaler device only. Do NOT swallow the capsules. Always use the new inhaler in the new carton. Do not save or use inhalers from previous cartons.
Healthcare providers should instruct the patient on proper use of the inhaler device.
Ensure hands are clean and dry and find a clean, dry surface to gather supplies and prepare dose. Check the expiration date and discard any expired product.
Inhaler preparation:
Remove the blue cap by pulling it straight off of the inhaler and place the cap to the side for later use.
Twist and pull off the mouthpiece to separate it from the handle.
Capsule preparation:
Just prior to use, remove 1 capsule from packaging by carefully peeling back the foil.
Do NOT try to push the capsule through the back of the foil package. Only remove 1 capsule at a time.
Discard any capsule that looks crushed, damaged, or wet.
Preparation of capsule with inhaler:
Hold the inhaler upright using the handle.
Drop 1 capsule into the opening of the capsule chamber. Do not load 2 capsules at the same time.
Line up the white arrows on the handle and mouthpiece.
Firmly push the mouthpiece and handle together until you hear a "click". This punctures the capsule.
Release the mouthpiece, which will spring back and stay attached. The inhaler is now ready to use.
Do not push the handle and mouthpiece together more than 1 time since the capsule may become damaged and the full dose may not be received.
If the capsule becomes damaged, discard it in the trash and begin with a new capsule.
Ensure the mouthpiece is securely attached and will not fall off before taking the dose.
Dose administration (patient instructions):
Stand or sit with your head and chest upright.
Hold the inhaler level and away from the mouth.
Breathe out completely. Do NOT breathe into the mouthpiece.
While keeping the inhaler level, close your lips firmly around the mouthpiece.
Take in a deep, comfortable breath until your lungs feel full. This normally takes several seconds.
As you breathe in, you will hear and feel the capsule "whirl" (spin). The whirl means the inhaler is working.
If you cough or stop inhaling the dose, start again using the same capsule.
After inhaling the dose, remove inhaler from your mouth and hold your breath for 5 seconds, then breathe out.
Twist and pull off the mouthpiece and take out the used capsule.
Repeat steps for second capsule, to complete the full dose.
Capsule disposition: After each use, discard the used capsules in the trash. Do NOT store capsules in the inhaler for future use.
Inhaler disposition: Ensure there are no capsules in the inhaler before storing for the next use. Attach the mouthpiece to the handle by pushing until you hear a "click". Attach the blue cap over the mouthpiece. Store for next use. Discard the inhaler after all of the capsules in the package have been used.
Cleaning the inhaler: It is normal for some powder to remain on the inhaler. Cleaning the inhaler is not necessary; however, a dry cotton swab or a dry tissue may be used to wipe the inside or outside of the mouthpiece.
Refer to the "Instructions for Use" section of the product labeling for detailed visual aids that accompany the written instructions.

akinesia / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
suicidal ideation / Delayed / Incidence not known
seizures / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
agranulocytosis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
ocular hypertension / Delayed / Incidence not known
neuroleptic malignant syndrome-like symptoms / Delayed / Incidence not known
skin cancer / Delayed / Incidence not known

skin laceration / Delayed / 2.0-2.0
chest pain (unspecified) / Early / 0-2.0
dyskinesia / Delayed / 10.0
myoclonia / Delayed / Incidence not known
dystonic reaction / Delayed / Incidence not known
involuntary movements / Delayed / Incidence not known
akathisia / Delayed / Incidence not known
trismus / Delayed / Incidence not known
bullous rash / Early / Incidence not known
depression / Delayed / Incidence not known
euphoria / Early / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
hallucinations / Early / Incidence not known
delirium / Early / Incidence not known
confusion / Early / Incidence not known
psychosis / Early / Incidence not known
ataxia / Delayed / Incidence not known
memory impairment / Delayed / Incidence not known
constipation / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
teeth grinding (bruxism) / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
glycosuria / Early / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
hypertension / Early / Incidence not known
phlebitis / Rapid / Incidence not known
palpitations / Early / Incidence not known
hypotension / Rapid / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
dyspnea / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
urinary retention / Early / Incidence not known
priapism / Early / Incidence not known
urinary incontinence / Early / Incidence not known
hematuria / Delayed / Incidence not known
sudden sleep onset / Delayed / Incidence not known
impulse control symptoms / Delayed / Incidence not known
hot flashes / Early / Incidence not known
edema / Delayed / Incidence not known
blepharospasm / Early / Incidence not known
blurred vision / Early / Incidence not known

cough / Delayed / 15.0-15.0
infection / Delayed / 0-6.0
nausea / Early / 5.0-5.0
vomiting / Early / 3.0-3.0
pharyngitis / Delayed / 3.0-3.0
headache / Early / 2.0-2.0
insomnia / Early / 2.0-2.0
pruritus / Rapid / Incidence not known
purpura / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
flushing / Rapid / Incidence not known
rash / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
abnormal dreams / Early / Incidence not known
tremor / Early / Incidence not known
paranoia / Early / Incidence not known
paresthesias / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
restlessness / Early / Incidence not known
agitation / Early / Incidence not known
nightmares / Early / Incidence not known
dizziness / Early / Incidence not known
hiccups / Early / Incidence not known
diarrhea / Early / Incidence not known
dyspepsia / Early / Incidence not known
weight gain / Delayed / Incidence not known
xerostomia / Early / Incidence not known
weight loss / Delayed / Incidence not known
anorexia / Delayed / Incidence not known
hypersalivation / Early / Incidence not known
dysgeusia / Early / Incidence not known
flatulence / Early / Incidence not known
syncope / Early / Incidence not known
urine discoloration / Early / Incidence not known
hoarseness / Early / Incidence not known
vitamin B6 deficiency / Delayed / Incidence not known
increased urinary frequency / Early / Incidence not known
drowsiness / Early / Incidence not known
asthenia / Delayed / Incidence not known
fatigue / Early / Incidence not known
abdominal pain / Early / Incidence not known
malaise / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
back pain / Delayed / Incidence not known
mydriasis / Early / Incidence not known
diplopia / Early / Incidence not known

INBRIJA

Rx

Aromatic amine that is metabolized to dopamine
First-line oral treatment option in combination with carbidopa for motor symptoms in Parkinson's disease
Available for oral inhalation for "as needed" use for 'off' episodes in Parkinson's patients receiving levodopa/carbidopa

Inhale the contents of 2 capsules (42 mg per capsule for a total of 84 mg) via oral inhalation with the provided inhaler as needed for 'off' symptoms up to 5 times daily. The dose should be taken when symptoms of an 'off' period start to return. DO NOT swallow the capsules; only use with the inhaler provided by the manufacturer. Max: 420 mg/day via oral inhalation.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Alfentanil: (Major) Prior to general anesthesia, levodopa may be continued as long as the patient is permitted to take oral medication. If levodopa-based therapy is interrupted temporarily, the usual daily dosage may be reinstituted or titrated upward to the normal dosage as soon as the patient is able to take oral medications. The patient should be observed for symptoms resembling neuroleptic malignant syndrome, and the usual regimen should be administered as soon as the patient is able to take oral medication.
Amantadine: (Minor) Amantadine can increase the efficiency of levodopa by its action on central nerve terminals.
Amisulpride: (Major) Avoid using these drugs together. Amisulpride is a central dopamine antagonist and can antagonize the actions of dopamine agonists such as levodopa. Amisulpride is generally used perioperatively to prevent and treat postoperative nausea and vomiting. Prior to general anesthesia, levodopa may be continued as long as the patient is permitted to take oral medication. If levodopa-based therapy is interrupted temporarily, the usual daily dosage may be reinstituted or titrated upward to the normal dosage as soon as the patient is able to take oral medications.
Amoxapine: (Moderate) Amoxapine exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Angiotensin II receptor antagonists: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Angiotensin-converting enzyme inhibitors: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Atropine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Atropine; Difenoxin: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
atypical antipsychotic: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Belladonna; Opium: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Benzphetamine: (Major) Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions or discontinuation of benzphetamine is recommended if the two agents are used concurrently.
Benztropine: (Minor) Through its central antimuscarinic actions, antimuscarinics such as benztropine can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if benztropine is added.
Beta-blockers: (Moderate) Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Bupropion: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Bupropion; Naltrexone: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Calcium-channel blockers: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Central-acting adrenergic agents: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Chlorpromazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Clonidine: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Cocaine: (Major) Concomitant use of cocaine with levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) can result in an increase in the risk of developing cardiac arrhythmias. Levodopa should be used cautiously in patients who are known users of cocaine. Conversely, electrocardiographic monitoring should be considered when using cocaine in patients receiving levodopa.
Codeine; Phenylephrine; Promethazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Codeine; Promethazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Dacarbazine, DTIC: (Moderate) Levodopa response may be decreased during chemotherapy with dacarbazine, DTIC. If dacarbazine is used in a patient stabilized on levodopa therapy, practitioners may wish to be alert for needed adjustments in the levodopa regimen to maintain patient status.
Darifenacin: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
Dextromethorphan; Bupropion: (Moderate) Use bupropion and levodopa with caution and monitor for CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness, which may result from cumulative dopamine agonist effects.
Dicyclomine: (Minor) Anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diphenoxylate; Atropine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Doxazosin: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Droperidol: (Major) Droperidol, a butyrophenone derivative, is a dopamine D2 receptor antagonist and thus, may reduce the therapeutic effects of levodopa, which is an agonist at dopamine D2 receptors. Avoidance of droperidol use in a patient with Parkinson's disease may be advisable unless the benefit of droperidol outweighs the risk of CNS depressive effects and decreased therapeutic response to dopamine agonists.
Eplerenone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Epoprostenol: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Esketamine: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as levodopa, and CNS depressants, such as esketamine. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Ferric Maltol: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Fluphenazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions. (Major) Many levodopa products may be taken with or without food. Follow the directions of the product prescribed. However, foods with a high protein content may delay or impair the oral absorption of levodopa and may reduce efficacy. The Parkinson's Foundation states that most patients have no problem taking levodopa-containing products with meals, but some experience less benefit if they take such products with a stomach full of protein (including meats, cheeses and other dairy products). When this occurs, it is recommended to only take carbidopa/levodopa along with non-protein foods. For patients with more advanced PD, it is best to take levodopa-containing medications 30 to 60 minutes before eating a meal to limit food interference. If nausea occurs, the products may be taken with a small non-protein snack, such as fruit or a cracker, to help. (Major) Patients with Parkinson's disease should avoid foods high in fat around the time of taking carbidopa; levodopa. These foods may delay gastric emptying, which can decrease and delay the absorption of levodopa. (Major) Patients with Parkinson's disease should avoid foods high in fiber around the time of taking carbidopa; levodopa. These foods may delay gastric emptying, which can decrease and delay the absorption of levodopa.
Fosphenytoin: (Moderate) Monitor for loss of efficacy in during concomitant use of levodopa and fosphenytoin. The beneficial effects of levodopa in Parkinson disease have been reported to be revered by phenytoin.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and levodopa. Concomitant use of gabapentin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Glycopyrrolate; Formoterol: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Guanfacine: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Hyoscyamine: (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Iloprost: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Indacaterol; Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Iron Salts: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Iron: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Isocarboxazid: (Contraindicated) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as isocarboxazid. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertensive crisis and other adverse cardiovascular effects can occur. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
Isoflurane: (Major) If administered before halogenated anesthetics, levodopa without a concurrent decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthesia is required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Isoniazid, INH: (Major) Concurrent use of levodopa with drugs that have MAOI-type activity, such as isoniazid, INH should be avoided if possible. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertension and other adverse cardiovascular effects can occur.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Concurrent use of levodopa with drugs that have MAOI-type activity, such as isoniazid, INH should be avoided if possible. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertension and other adverse cardiovascular effects can occur.
Isoniazid, INH; Rifampin: (Major) Concurrent use of levodopa with drugs that have MAOI-type activity, such as isoniazid, INH should be avoided if possible. Levodopa, a catecholamine precursor, can lead to a relative catecholamine (e.g., dopamine, norepinephrine, and epinephrine) excess when combined with a MAOI. Hypertension and other adverse cardiovascular effects can occur.
Isoproterenol: (Major) Levodopa is the metabolic precursor to dopamine. Since a portion of administered levodopa is converted to dopamine peripherally, concomitant administration with isoproterenol should be used with caution as the risk of cardiovascular toxicity is increased.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and levodopa. Dosage adjustments of lemborexant and levodopa may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Linezolid: (Major) Concomitant use of levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) and drugs with monoamine oxidase inhibitor (MAOI) activity, such as linezolid, can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
Loop diuretics: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Loxapine: (Major) Due to opposing effects on central dopaminergic activity, loxapine and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to loxapine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may transiently elevate growth hormone concentrations, such as levodopa. Healthcare providers are advised to discontinue levodopa therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Maprotiline: (Moderate) Maprotiline exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Mecamylamine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Methamphetamine: (Major) Levodopa, due to its conversion to dopamine, may increase the risk of developing amphetamine-induced cardiac arrhythmias; dosage reductions of amphetamines are recommended if the two agents are used concurrently.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Methscopolamine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Methyldopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Metoclopramide: (Major) Metoclopramide is a central dopamine antagonist. Metoclopramide can antagonize the actions of dopamine agonists such as levodopa. In addition, metoclopramide may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Dyskinesias and other extrapyramidal effects have been reported during treatment with various anti-parkinson's medications, particularly levodopa. A symptom complex resembling neuroleptic malignant syndrome in association with rapid dose reduction, withdrawal of, or changes in anti-parkinsonian therapy has also been observed. The manufacturer of metoclopramide does not specifically contraindicate the use of metoclopramide and dopamine agonists; however, coadministration should be avoided if possible.
Metyrosine: (Major) The extrapyramidal effects of metyrosine can antagonize the effects of levodopa. Dosage adjustments of either of these medications may be required.
Molindone: (Major) Due to opposing effects on central dopaminergic activity, molindone and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Animal studies have not shown increased toxicity when molindone is given concurrently with representative members of the antiparkinson drugs class.
Nabilone: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as levodopa, and CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Neostigmine; Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with levodopa may decrease levodopa serum concentrations. If coadministration is necessary, monitor clinical response to levodopa and increase levodopa dose accordingly.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Oliceridine: (Major) Concomitant use of oliceridine with levodopa may cause excessive sedation and somnolence. Limit the use of oliceridine with levodopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Oxybutynin: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
Papaverine: (Major) The beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by coadministration of papaverine; avoid concurrent use in these patients. Papaverine may block dopamine receptors in the striatum and result in loss of control of Parkinson's disease in patients who are taking levodopa.
Perphenazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Perphenazine; Amitriptyline: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Phenelzine: (Contraindicated) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as phenelzine, due to increased risk of hypertensive crisis. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added. (Minor) Through its central antimuscarinic actions, hyoscyamine can potentiate the dopaminergic effects of levodopa. Clinicians should be ready to decrease doses of levodopa if hyoscyamine is added.
Phenothiazines: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Phenoxybenzamine: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Phenytoin: (Moderate) Monitor for loss of efficacy in during concomitant use of levodopa and phenytoin. The beneficial effects of levodopa in Parkinson disease have been reported to be revered by phenytoin.
Pimozide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Polysaccharide-Iron Complex: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure during concomitant levodopa and potassium-sparing diuretic use due to risk for additive hypotension; a potassium-sparing diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Pramipexole: (Minor) Pramipexole increases the Cmax of levodopa and decreases Tmax from 2.5 to 0.5 hrs.
Prazosin: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and levodopa. Concomitant use of pregabalin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Procarbazine: (Major) Concomitant use of levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity (e.g., procarbazine) can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
Prochlorperazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Promethazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Promethazine; Dextromethorphan: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Promethazine; Phenylephrine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Propantheline: (Moderate) Anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Propofol: (Major) If administered before halogenated anesthetics, levodopa without concomitant use of a decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthetics are required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Pyridoxine, Vitamin B6: (Moderate) Monitor for reduced levodopa efficacy during concomitant use of pyridoxine (vitamin B6). Pyridoxine, in doses as low as 10 mg/day, may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine.
Rasagiline: (Moderate) There may be some increase in rasagiline blood levels in the presence of levodopa, the effect is modest and rasagiline dosing need not be modified in the presence of carbidopa; levodopa. Rasagiline and carbidopa; levodopa are frequently used together; however, there is the possibility of increased dyskinesia and postural hypotension when combined.
Rotigotine: (Moderate) In clinical studies, concurrent use of L-dopa/carbidopa with rotigotine had no effect on the pharmacokinetics of either agent. However, rotigotine may potentiate the dopaminergic side effects of levodopa via a pharmacodynamic interaction. Subsequent worsening of pre-existing dyskinesias may occur.
Safinamide: (Moderate) Safinamide and carbidopa; levodopa are indicated for use in combination; however, there is the possibility of new onset dyskinesias or exacerbation of pre-existing dyskinesias. Patients should be advised to contact their health care provider if they notice new or worsening dyskinesias while taking these medicines together.
Sapropterin: (Major) Coadministration of sapropterin and levodopa has been associated with seizures. Post-marketing safety surveillance showed 3 patients (all with underlying neurologic disorder) develop convulsions, exacerbation of convulsions, over-stimulation, or irritability while receiving concomitant levodopa and sapropterin.
Scopolamine: (Minor) The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
Selegiline: (Moderate) Monitor blood pressure during concomitant use of levodopa and selegiline. Concomitant use of levodopa with selective MAO-B inhibitors may be associated with orthostatic hypotension.
Sevoflurane: (Major) If administered before halogenated anesthetics, levodopa without a concurrent decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthesia is required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Administration of iron salts, including polysaccharide-iron complex or multivitamins containing iron, should be separated from oral levodopa by at least 2 hours to avoid reduction in levodopa efficacy. Iron salts may reduce the bioavailability of levodopa and carbidopa; levodopa products.
Solifenacin: (Minor) Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. Antimuscarinics, by slowing GI transit, may also decrease levodopa bioavailability; however, this mechanism appears to be of modest clinical significance. Antimuscarinic agents targeted specifically for urinary incontinence may be less likely to produce pronounced effects on levodopa response than those with more pronounced systemic action.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as levodopa. Caution is recommended since this combination has not been evaluated.
Tedizolid: (Major) Concomitant use of levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity (e.g., tedizolid) can result in hypertensive crisis or unstable blood pressure changes. Simultaneous use of these agents should be avoided if possible.
Tetrabenazine: (Moderate) Monitor for a decrease in levodopa efficacy during concomitant tetrabenazine use. Levodopa and tetrabenazine may antagonize each other's effects: levodopa is metabolized to dopamine while tetrabenazine depletes dopamine stores and acts as a dopamine receptor blocker. While concomitant use is generally not recommended for this reason, combination therapy may be beneficial in the management of some levodopa-related dyskinesias.
Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant levodopa and thiazide diuretic use due to risk for additive hypotension; a thiazide diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Thioridazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Tranylcypromine: (Contraindicated) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as tranylcypromine, due to the increased risk of hypertensive crisis. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
Treprostinil: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Tricyclic antidepressants: (Moderate) Monitor blood pressure and for symptoms of dyskinesia during concomitant levodopa and tricyclic antidepressant use. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use.
Trifluoperazine: (Major) Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Due to opposing effects on central dopaminergic activity, phenothiazines and levodopa may interfere with the effectiveness of each other.
Trihexyphenidyl: (Minor) The doses of trihexyphenidyl and levodopa may need to be adjusted when the drugs are given simultaneously. Trihexyphenidyl can potentiate the dopaminergic effects of levodopa.
Vasodilators: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.

INBRIJA Respiratory (Inhalation) Pwd: 42mg

Generally, 8 grams/day PO; 420 mg/day via oral inhalation.

Generally, 8 grams/day PO; 420 mg/day via oral inhalation.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Levodopa is the amino acid precursor of dopamine. Unlike dopamine, levodopa crosses the blood-brain barrier, although the method of administration is important for the effectiveness of the drug in disorders of central degeneration of dopaminergic neurons such as Parkinson's disease.
 
When levodopa is administered orally, it is rapidly decarboxylated to dopamine in the periphery leaving only a small portion of levodopa for diffusion into the central nervous system (CNS). Carbidopa is required in combination with levodopa for optimal oral therapy since carbidopa inhibits the peripheral breakdown of levodopa, making more levodopa available for delivery into the CNS.
 
Levodopa oral inhalation diffuses directly into the CNS where it is converted to dopamine. Disease progression is associated with 'off' episodes, which occur between routine doses of carbidopa; levodopa when the medication benefits wear off and motor symptoms re-emerge. Intermittent use of levodopa treats these episodes, which are thought to result from loss of ability to store dopamine, and possibly from changes in peripheral levodopa pharmacokinetics or postsynaptic dopamine functioning.

Levodopa is administered orally and by oral inhalation. When levodopa is administered orally, it is rapidly decarboxylated in extracerebral tissues to dopamine, leaving only a small portion of a dose to be transported unchanged into the central nervous system. The plasma half-life of oral levodopa is about 50 minutes. When levodopa is administered with carbidopa, the half-life is increased to 1.5 hours. The half-life of levodopa following a single orally inhaled dose (84 mg) is 2.3 hours. The two major metabolic pathways are decarboxylation by dopa decarboxylase and O-methylation by catechol-O-methyltransferase (COMT). Levodopa is excreted in the urine primarily as metabolites, including dopamine and homovanillic acid (HVA). Carbidopa reduces the amount of levodopa required for a given response by about 75% and decreases plasma and urinary dopamine and HVA.
 
Affected Cytochrome P450 isoenzymes and drug transporters: None

Following oral administration, amino acid transport mechanisms carry levodopa across the membrane of the gastrointestinal tract. Levodopa competes with certain amino acids for transport across the gut wall; therefore, the absorption of levodopa may be impaired in those on a high protein diet. Any food (i.e., high fat or high protein) or drug that delays gastric emptying may decrease the absorption of levodopa. Iron salts or multivitamins containing iron salts can form chelates with levodopa and reduce the bioavailability of levodopa.

Following oral inhalation of one 84-mg dose of levodopa, the median time to maximum plasma concentrations of levodopa is about 0.5 hours (range: 0.17 to 2 hours). In fasting healthy volunteers, the bioavailability of levodopa is about 70% relative to immediate-release oral levodopa tablets. The dose-normalized maximum concentration from orally inhaled levodopa is about 50% of that following immediate-release oral tablets.

Levodopa should be used in pregnancy only if the potential benefit outweighs the potential risk to the fetus. There are no adequate or well-controlled studies regarding the developmental risks to the fetus from levodopa use during human pregnancy. Levodopa/carbidopa therapy has been shown to be developmentally toxic in animal studies. When administered to pregnant rabbits throughout organogenesis, the combination caused both visceral and skeletal malformations in rabbits. No teratogenic effects were observed when carbidopa/levodopa was administered to pregnant mice; there was a decrease in the number of live pups delivered by rats receiving carbidopa/levodopa during organogenesis. Levodopa crosses the placenta in humans and reaches levels in the fetus comparable to maternal blood, although pregnancy outcomes have been primarily unremarkable. Two miscarriages were reported in the first trimester during use of carbidopa/levodopa, and one infant exposed to levodopa in utero was reported to have osteomalacia. One case of neonatal seizure occurred after use of bromocriptine plus carbidopa/levodopa/entacapone during pregnancy.  Maternal complications reported in three pregnancies during use of levodopa in combination with carbidopa included first trimester vaginal bleeding, third trimester nausea and vomiting, depression, and preeclampsia. The effects of levodopa in labor and delivery are unknown. One case describes a patient who became pregnant on two separate occasions while receiving levodopa and cabergoline for Parkinson's disease. The medications were continued throughout the pregnancies. There were no fetal complications; however, cesarean section was required in the second birth due to placental abruption.

Excretion of levodopa into human breast milk has been reported, and caution is advisable in breast-feeding mothers. Because levodopa can inhibit prolactin secretion, interference with proper lactation is possible; however, there are limited data about this potential in lactating women. Partial to complete suppression of lactation has been observed in female patients given levodopa for galactorrhea. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[48681]& [48683] [63854] If levodopa must be administered during breast-feeding, the infant should be monitored for commonly encountered adverse effects associated with dopaminergic therapy including dyskinesias, insomnia, sedation, nausea, and constipation. In one case report of a breast-feeding mother with Parkinson's disease receiving sustained-release carbidopa/levodopa 50/200 mg 4 times daily, peak levels of levodopa in milk occurred 3 hours after a dose and returned to baseline after 6 hours. After receiving the same dose of the immediate-release (IR) formulation, similar results were observed, with the exception of higher milk: plasma ratios with the IR product (0.32 vs. 0.28). The infant ingested 0.127 mg and 0.181 mg of levodopa after maternal intake of the sustained-release and immediate-release products, respectively. It was estimated that the infant received an average of 0.3% of the maternal weight-adjusted dosage of the sustained release product and 0.5% of the maternal weight-adjusted dose of the immediate-release product. No adverse effects were observed in her infant, whose development was normal at 2 years of age.[48662]