This combination capsule is indicated for the treatment of Parkinson's disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Levodopa: Levodopa is the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson's disease.

Carbidopa: When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. Carbidopa inhibits the decarboxylation of peripheral levodopa, making more levodopa available for delivery to the brain.

Dosage in Patients Naive to Levodopa Therapy: The recommended starting dosage of RYTARY in levodopa-naive patients is RYTARY 95 mg taken orally three times a day for the first 3 days. On the fourth day of treatment, the dosage of RYTARY may be increased to 145 mg taken three times a day. Based upon individual patient clinical response and tolerability, the RYTARY dose may be increased up to a maximum recommended dose of 390 mg taken three times a day. The dosing frequency may be changed from three times a day to a maximum of five times a day if more frequent dosing is needed and if tolerated. Maintain patients on the lowest dosage required to achieve symptomatic control and to minimize adverse reactions such as dyskinesia and nausea. The maximum recommended daily dose of RYTARY is 2450 mg.

Converting from Immediate-Release Carbidopa-Levodopa to RYTARY: The dosages of other carbidopa and levodopa products are not interchangeable on a 1:1 basis with the dosages of RYTARY. To convert patients from immediate-release carbidopa-levodopa to RYTARY, first calculate the patient’s current total daily dose of levodopa. The starting total daily dose of RYTARY is as recommended in below mentioned chart. After conversion, any combination of the four RYTARY dosage strengths can be used to achieve an optimal dosing. Adjust the dose and dosing frequency as necessary to maintain patient tolerance and sufficient symptomatic control. Administration of concomitant Parkinson’s disease medications should remain stable while adjusting the RYTARY dose. In clinical trials, RYTARY was administered in divided doses of three to five times a day. The maximum recommended total daily dose of RYTARY is 612.5 mg / 2,450 mg. For patients currently treated with carbidopa and levodopa plus a catechol-O-methyl transferase (COMT) inhibitor (such as entacapone), the initial total daily dose of levodopa in RYTARY described in Table 1 may need to be increased. Use of RYTARY in combination with other levodopa products has not been studied.

Conversion from Immediate Release Carbidopa-Levodopa to RYTARY-

Total daily dose of Levodopa in immediate release Levodopa-carbidopa	Total daily dose of Levodopa in Levodopa-Carbidopa	Levodopa-Carbidopa dosing regimen
400 mg to 549 mg	855 mg	3 capsules RYTARY 95 mg taken TID
550 mg to 749 mg	1140 mg	4 capsules RYTARY 95 mg taken TID
750 mg to 949 mg	1305 mg	3 capsules RYTARY 145 mg taken TID
950 mg to 1249 mg	1755 mg	3 capsules RYTARY 195 mg taken TID
Equal to or greater than 1250 mg	2340 mg or 2205 mg	3 capsules RYTARY 245 mg taken TID

Iron salts and dopamine D2 antagonists including metoclopramide: May reduce the effectiveness of RYTARY.

This preparation is contraindicated in patients who are currently taking a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine) or have recently (within 2 weeks) taken a nonselective MAO inhibitor. Hypertension can occur if these drugs are used concurrently.

Early Parkinson’s disease: Most common adverse reactions (incidence ≥ 5% and greater than placebo) are nausea, dizziness, headache, insomnia, abnormal dreams, dry mouth, dyskinesia, anxiety, constipation, vomiting, and orthostatic hypotension.

Advanced Parkinson’s disease: Most common adverse reactions (incidence ≥5% and greater than oral immediate-release carbidopa-levodopa) are nausea and headache.

Pregnancy: There are no adequate data on the developmental risk associated with the use of RYTARY in pregnant women. In animal studies, carbidopa-levodopa has been shown to be developmentally toxic (including teratogenic effects) at clinically relevant doses.

Lactation: Levodopa has been detected in human milk after administration of carbidopa-levodopa. There are no data on the presence of carbidopa in human milk, the effects of levodopa or carbidopa on the breastfed infant, or the effects on milk production. However, inhibition of lactation may occur because levodopa decreases secretion of prolactin in humans. Carbidopa is excreted in rat milk.

Falling Asleep During Activities of Daily Living and Somnolence, Withdrawal-Emergent Hyperpyrexia and Confusion (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), Cardiovascular Ischemic Events, Hallucinations/Psychosis, Impulse Control/ Compulsive Behaviors, Dyskinesia, Peptic Ulcer Disease, Glaucoma, etc.

Pediatric use: Safety and effectiveness in pediatric patients have not been established.

Store in a cool and dry place, keep away from light and children.