CARBIDOPA AND LEVODOPA tablet

1. No Title 1572549740
2. No Title 1572549794
3. No Title 1572550401
4. No Title 1572552638
5. No Title 1572553020
6. Carbidopa And Levodopa Tablets, Usp10mg/100mg, 25mg/100mg And 25mg/250mgrx Onlyoctober 2011
7. Carbidopa And Levodopa Tablets Usp
8. Principal Display Panel - 100 Tablet Bottle Label
9. Principal Display Panel - 10 Mg/100 Mg Tablet Bottle Label
10. Principal Display Panel - 25 Mg/100 Mg Tablet Bottle Label
11. Principal Display Panel - 25 Mg/250 Mg Tablet Bottle Label
12. Carbidopa And Levodopa Tablets, Usp
13. Description
14. Clinical Pharmacology
15. Indications And Usage
16. Contraindications
17. Warnings
18. Precautions
19. Adverse Reactions
20. Overdosage
21. Dosage And Administration
22. How Supplied
23. Carbidopa And Levodopa Tablet
24. Package/label Display Panel 25mg/250mg
25. Description
26. Clinical Pharmacology
27. Indications And Usage
28. Contraindications
29. Warnings
30. Precautions
31. Adverse Reactions
32. Overdosage
33. Dosage And Administration
34. How Supplied
35. Package/label Display Panel
36. Repackaging Information
37. Principal Display Panel - 25/100mg
38. No Title 1572452792
39. Carbidopa And Levodopa
40. No Title 1572452810
41. No Title 1572453334
42. Package Label.principal Display Panel
43. Package Label.principal Display Panel
44. Principal Display Panel - 25mg / 100mg
45. No Title 1572456620
46. Packaging Information
47. Package/label Display Panel Carton - 25 Mg/100 Mg
48. Package/label Display Panel Blister - 25 Mg/100 Mg
49. Package/label Display Panel Carton - 25 Mg/250 Mg
50. Package/label Display Panel Blister - 25 Mg/250 Mg
51. Principal Display Panel-25 Mg/100 Mg
52. No Title 1572448644
53. Principal Display Panel
54. Carbidopa And Levodopa Tablets, Usp
55. Package/label Display Panel

No Title 1572549740 ⮝

40-9182
Revised September 2011

Rx Only

No Title 1572549794 ⮝

40-9267

Revised January 2016

Rx Only

No Title 1572550401 ⮝

40-8774

Revised January 2010

Rx Only

No Title 1572552638 ⮝

40-9182

Revised February 2016

Rx Only

No Title 1572553020 ⮝

40-9182

Revised February 2016

Rx Only

Carbidopa And Levodopa Tablets, Usp10mg/100mg, 25mg/100mg And 25mg/250mgrx Onlyoctober 2011 ⮝

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63739-046(NDC:0093-0292) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code 93;292 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:63739-046-10 10 in 1 BOX, UNIT-DOSE 03/01/1993 04/30/2019 1 10 in 1 BLISTER PACK; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073618 03/01/1993 04/30/2019

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63739-047(NDC:0093-0293) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8)

Product Characteristics Color YELLOW (mottled-yellow) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code 93;293;TEVA Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:63739-047-10 10 in 1 BOX, UNIT-DOSE 04/01/1993 04/30/2019 1 10 in 1 BLISTER PACK; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073589 04/01/1993 04/30/2019

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63739-048(NDC:0093-0294) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 10 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code 93;294 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:63739-048-10 10 in 1 BOX, UNIT-DOSE 01/01/1993 1 10 in 1 BLISTER PACK; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073607 01/01/1993

Labeler - McKesson Corporation dba SKY Packaging (140529962)

Establishment
Name	Address	ID/FEI	Business Operations
McKesson Corporation dba RX Pak		025183281	REPACK(63739-046, 63739-047, 63739-048)

Revised: 5/2019 Document Id: 51962452-1356-4b1e-99a8-3c22cace037c 34391-3 Set id: 8edc4a14-f8b2-48cf-8478-ed51f2047d27 Version: 13 Effective Time: 20190525 McKesson Corporation dba SKY Packaging

Carbidopa And Levodopa Tablets Usp ⮝

Rx only
Rev. V 6/2016
322K019800716

Principal Display Panel - 100 Tablet Bottle Label ⮝

NDC 51862-077-01

Carbidopa and
Levodopa
Tablets USP
10 mg/100 mg

Rx only

100 TABLETS

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51862-077 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 10 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code 93;292 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51862-077-01 100 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 10/24/2016 08/31/2019 2 NDC:51862-077-05 500 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 10/24/2016 03/31/2020

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073618 10/24/2016 03/31/2020

Labeler - Mayne Pharma Inc (867220261)

Establishment
Name	Address	ID/FEI	Business Operations
Teva Pharmaceutical Industries Ltd.		533065814	ANALYSIS(51862-077) , MANUFACTURE(51862-077) , LABEL(51862-077) , PACK(51862-077)

Establishment
Name	Address	ID/FEI	Business Operations
Teva Pharmaceutical Industries Ltd.		533065822	ANALYSIS(51862-077)

Establishment
Name	Address	ID/FEI	Business Operations
Teva Pharmaceutical Industries Ltd.		533065806	ANALYSIS(51862-077) , MANUFACTURE(51862-077) , LABEL(51862-077) , PACK(51862-077)

Revised: 5/2019 Document Id: 34c0f632-3f88-47cc-971a-f710ad62f939 34391-3 Set id: 1f457767-5a67-43c6-9ed1-1e707fc474f0 Version: 3 Effective Time: 20190523 Mayne Pharma Inc

Principal Display Panel - 10 Mg/100 Mg Tablet Bottle Label ⮝

NDC 51862-855-01

Carbidopa
and Levodopa
Tablets, USP

10 mg/100 mg

Rx Only

100 Tablets

mayne pharma

Principal Display Panel - 25 Mg/100 Mg Tablet Bottle Label ⮝

NDC 51862-856-01

Carbidopa
and Levodopa
Tablets, USP

25 mg/100 mg

Rx Only

100 Tablets

mayne pharma

Principal Display Panel - 25 Mg/250 Mg Tablet Bottle Label ⮝

NDC 51862-858-01

Carbidopa
and Levodopa
Tablets, USP

25 mg/250 mg

Rx Only

100 Tablets

mayne pharma

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51862-855 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Carbidopa (UNII: MNX7R8C5VO) (Carbidopa Anhydrous - UNII:KR87B45RGH) Carbidopa Anhydrous 10 mg Levodopa (UNII: 46627O600J) (Levodopa - UNII:46627O600J) Levodopa 100 mg

Inactive Ingredients Ingredient Name Strength Magnesium Stearate (UNII: 70097M6I30) Microcrystalline Cellulose (UNII: OP1R32D61U) Starch, Corn (UNII: O8232NY3SJ) FD&C Blue No. 2 (UNII: L06K8R7DQK)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code m;711 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51862-855-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 07/16/2018 2 NDC:51862-855-05 500 in 1 BOTTLE; Type 0: Not a Combination Product 07/16/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073618 07/16/2018

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51862-856 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Carbidopa (UNII: MNX7R8C5VO) (Carbidopa Anhydrous - UNII:KR87B45RGH) Carbidopa Anhydrous 25 mg Levodopa (UNII: 46627O600J) (Levodopa - UNII:46627O600J) Levodopa 100 mg

Inactive Ingredients Ingredient Name Strength Magnesium Stearate (UNII: 70097M6I30) Microcrystalline Cellulose (UNII: OP1R32D61U) Starch, Corn (UNII: O8232NY3SJ) D&C Yellow No. 10 (UNII: 35SW5USQ3G) FD&C Yellow No. 6 (UNII: H77VEI93A8)

Product Characteristics Color YELLOW (mottled-yellow) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code m;721 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51862-856-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 07/16/2018 2 NDC:51862-856-05 500 in 1 BOTTLE; Type 0: Not a Combination Product 07/16/2018 3 NDC:51862-856-10 1000 in 1 BOTTLE; Type 0: Not a Combination Product 07/16/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073589 07/16/2018

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51862-858 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Carbidopa (UNII: MNX7R8C5VO) (Carbidopa Anhydrous - UNII:KR87B45RGH) Carbidopa Anhydrous 25 mg Levodopa (UNII: 46627O600J) (Levodopa - UNII:46627O600J) Levodopa 250 mg

Inactive Ingredients Ingredient Name Strength Magnesium Stearate (UNII: 70097M6I30) Microcrystalline Cellulose (UNII: OP1R32D61U) Starch, Corn (UNII: O8232NY3SJ) FD&C Blue No. 2 (UNII: L06K8R7DQK)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code m;731 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51862-858-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 07/16/2018 2 NDC:51862-858-05 500 in 1 BOTTLE; Type 0: Not a Combination Product 07/16/2018 3 NDC:51862-858-10 1000 in 1 BOTTLE; Type 0: Not a Combination Product 07/16/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073607 07/16/2018

Labeler - Mayne Pharma Inc. (867220261)

Establishment
Name	Address	ID/FEI	Business Operations
Mayne Pharma International Pty Ltd		756003745	MANUFACTURE(51862-855, 51862-856, 51862-858) , ANALYSIS(51862-855, 51862-856, 51862-858)

Establishment
Name	Address	ID/FEI	Business Operations
Mayne Pharma Inc.		867220261	ANALYSIS(51862-855, 51862-856, 51862-858) , PACK(51862-855, 51862-856, 51862-858) , LABEL(51862-855, 51862-856, 51862-858)

Revised: 10/2018 Document Id: 927c1f46-e928-41a2-945f-08e06cca99d4 34391-3 Set id: d92bf9c8-ec59-4a7d-996f-2727d6e6adc5 Version: 3 Effective Time: 20181022 Mayne Pharma Inc.

Carbidopa And Levodopa Tablets, Usp ⮝

Rx Only

Description ⮝

Carbidopa and levodopa is a combination product for the treatment of Parkinson's disease and syndrome.

Carbidopa, USP an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.25. It is designated chemically as (-)-L- -hydrazino- -methyl- -(3,4-dihydroxybenzene) propanoic acid monohydrate. Its molecular formula is C 10H 14N 2O 4.H 2O, and its structural formula is:

Tablet content is expressed in terms of anhydrous carbidopa which has a molecular weight of 226.23.

Levodopa, USP an aromatic amino acid, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 197.19. It is designated chemically as (-)-L- -amino- -(3,4-dihydroxybenzene) propanoic acid. Its molecular formula is C 9H 11NO 4, and its structural formula is:

Carbidopa and levodopa tablets, USP for oral administration, are supplied in three strengths:

10 mg/100 mg, containing 10 mg of carbidopa and 100 mg of levodopa.

25 mg/100 mg, containing 25 mg of carbidopa and 100 mg of levodopa.

25 mg/250 mg, containing 25 mg of carbidopa and 250 mg of levodopa.

In addition, each tablet contains the following inactive ingredients:
10 mg/100 mg Corn starch, FD&C blue #2 aluminum lake, magnesium stearate, microcrystalline cellulose, and pregelatinized starch (maize).

25 mg/100 mg Corn starch, D&C yellow #10 aluminum lake, FD&C yellow #6 aluminum lake (sunset yellow lake), magnesium stearate, microcrystalline cellulose, and pregelatinized starch (maize).

25 mg/250 mg Corn starch, FD&C blue #2 aluminum lake, magnesium stearate, microcrystalline cellulose, and pregelatinized starch (maize).

Clinical Pharmacology ⮝

Mechanism of Action: Parkinson's disease is a progressive, neurodegenerative disorder of the extrapyramidal nervous system affecting the mobility and control of the skeletal muscular system. Its characteristic features include resting tremor, rigidity, and bradykinetic movements. Symptomatic treatments, such as levodopa therapies, may permit the patient better mobility.

Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier. However, levodopa, 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.

Pharmacodynamics: 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. For this reason, large doses of levodopa are required for adequate therapeutic effect, and these may often be accompanied by nausea and other adverse reactions, some of which are attributable to dopamine formed in extracerebral tissues.

Since levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be impaired in some patients on a high protein diet.

Carbidopa inhibits decarboxylation of peripheral levodopa. It does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system.

The incidence of levodopa-induced nausea and vomiting is less with the combination product than with levodopa. In many patients, this reduction in nausea and vomiting will permit more rapid dosage titration.

Since its decarboxylase inhibiting activity is limited to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available for transport to the brain.

Pharmacokinetics: Carbidopa reduces the amount of levodopa required to produce a given response by about 75% and, when administered with levodopa, increases both plasma levels and the plasma half-life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid.

The plasma half-life of levodopa is about 50 minutes, without carbidopa. When carbidopa and levodopa are administered together, the half-life of levodopa is increased to about 1.5 hours. At steady state, the bioavailability of carbidopa from carbidopa and levodopa tablets is approximately 99% relative to the concomitant administration of carbidopa and levodopa.

In clinical pharmacologic studies, simultaneous administration of carbidopa and levodopa produced greater urinary excretion of levodopa in proportion to the excretion of dopamine than administration of the two drugs at separate times.

Pyridoxine hydrochloride (vitamin B 6), in oral doses of 10 mg to 25 mg, may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine; therefore, carbidopa and levodopa can be given to patients receiving supplemental pyridoxine (vitamin B 6).

Special Populations
Geriatric: A study in eight young healthy subjects (21 to 22 yr) and eight elderly healthy subjects (69 to 76 yr) showed that the absolute bioavailability of levodopa was similar between young and elderly subjects following oral administration of levodopa and carbidopa. However, the systemic exposure (AUC) of levodopa was increased by 55% in elderly subjects compared to young subjects. Based on another study in forty patients with Parkinson s disease, there was a correlation between age of patients and the increase of AUC of levodopa following administration of levodopa and an inhibitor of peripheral dopa decarboxylase. AUC of levodopa was increased by 28% in elderly patients (greater than or equal to 65 yr) compared to young patients (less than 65 yr). Additionally, mean value of C max for levodopa was increased by 24% in elderly patients (greater than or equal to 65 yr) compared to young patients (less than 65 yr) (see PRECAUTIONS, Geriatric Use).

The AUC of carbidopa was increased in elderly subjects (n=10, 65 to 76 yr) by 29% compared to young subjects (n=24, 23 to 64 yr) following IV administration of 50 mg levodopa with carbidopa (50 mg). This increase is not considered a clinically significant impact.

Indications And Usage ⮝

Carbidopa and levodopa tablets, USP are indicated in the treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Carbidopa allows patients treated for Parkinson's disease to use much lower doses of levodopa. Some patients who responded poorly to levodopa have improved on carbidopa and levodopa. This is most likely due to decreased peripheral decarboxylation of levodopa caused by administration of carbidopa rather than by a primary effect of carbidopa on the nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa.

Carbidopa may also reduce nausea and vomiting and permit more rapid titration of levodopa.

Contraindications ⮝

Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with carbidopa and levodopa. These inhibitors must be discontinued at least two weeks prior to initiating therapy with this combination product. Carbidopa and levodopa may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl) (see PRECAUTIONS, Drug Interactions).

Carbidopa and levodopa is contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.

Warnings ⮝

When carbidopa and levodopa tablets are to be given to patients who are being treated with levodopa, levodopa must be discontinued at least twelve hours before therapy with the combination product is started. In order to reduce adverse reactions, it is necessary to individualize therapy. See DOSAGE AND ADMINISTRATION section before initiating therapy.

The addition of carbidopa with levodopa in the form of this combination product reduces the peripheral effects (nausea, vomiting) due to decarboxylation of levodopa; however, carbidopa does not decrease the adverse reactions due to the central effects of levodopa. Because carbidopa permits more levodopa to reach the brain and more dopamine to be formed, certain adverse central nervous system (CNS) effects, e.g., dyskinesias (involuntary movements), may occur at lower dosages and sooner with carbidopa and levodopa than with levodopa alone.

All patients should be observed carefully for the development of depression with concomitant suicidal tendencies.

Carbidopa and levodopa should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.

As with levodopa, care should be exercised in administering the combination product, to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment, in a facility with provisions for intensive cardiac care.

As with levodopa, treatment with the combination product may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.

Falling Asleep During Activities of Daily Living and Somnolence

Patients taking carbidopa and levodopa alone or with other dopaminergic drugs have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (includes operation of motor vehicles). Road traffic accidents attributed to sudden sleep onset have been reported. Although many patients reported somnolence while on dopaminergic medications, there have been reports of road traffic accidents attributed to sudden onset of sleep in which the patient did not perceive any warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Sudden onset of sleep has been reported to occur as long as one year after the initiation of treatment.

Falling asleep while engaged in activities of daily living usually occurs in patients experiencing preexisting somnolence, although some patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribers should be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Patients should be advised to exercise caution while driving or operating machines during treatment with carbidopa and levodopa. Patients who have already experienced somnolence or an episode of sudden sleep onset should not participate in these activities during treatment with carbidopa and levodopa.

Before initiating treatment with carbidopa and levodopa, advise patients about the potential to develop drowsiness and ask specifically about factors that may increase the risk for somnolence with carbidopa and levodopa such as the use of concomitant sedating medications and the presence of sleep disorders. Consider discontinuing carbidopa and levodopa in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.). If treatment with carbidopa and levodopa continues, patients should be advised not to drive and to avoid other potentially dangerous activities that might result in harm if the patients become somnolent. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

Hyperpyrexia and Confusion

Sporadic cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) have been reported in association with dose reductions or withdrawal of certain antiparkinsonian agents such as levodopa, carbidopa levodopa, or carbidopa levodopa extended release. Therefore, patients should be observed carefully when the dosage of levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.

NMS is an uncommon but life-threatening syndrome characterized by fever or hyperthermia. Neurological findings, including muscle rigidity, involuntary movements, altered consciousness, mental status changes; other disturbances, such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper-or hypotension; laboratory findings, such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin have been reported.

The early diagnosis of this condition is important for the appropriate management of these patients. Considering NMS as a possible diagnosis and ruling out other acute illnesses (e.g., pneumonia, systemic infection, etc.) is essential. This may be especially complex if the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.

The management of NMS should include: 1) intensive symptomatic treatment and medical monitoring and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene, are often used in the treatment of NMS; however, their effectiveness has not been demonstrated in controlled studies.

Precautions ⮝

General: As with levodopa, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended therapy.

Patients with chronic wide-angle glaucoma may be treated cautiously with carbidopa and levodopa provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.

Dyskinesia: Levodopa alone, as well as carbidopa and levodopa, is associated with dyskinesias. The occurrence of dyskinesias may require dosage reduction.

Hallucinations/Psychotic-Like Behavior: Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In general, hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa. Hallucinations may be accompanied by confusion and to a lesser extent sleep disorder (insomnia) and excessive dreaming.

Carbidopa and levodopa may have similar effects on thinking and behavior. This abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.

Ordinarily, patients with a major psychotic disorder should not be treated with carbidopa and levodopa, because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson s disease and may decrease the effectiveness of carbidopa and levodopa.

Impulse Control/Compulsive Behaviors: Reports of patients taking dopaminergic medications (medications that increase central dopaminergic tone), suggest that patients may experience an intense urge to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or the caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with carbidopa and levodopa. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa (see Information for Patients).

Melanoma: Epidemiological studies have shown that patients with Parkinson s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson s disease or other factors, such as drugs used to treat Parkinson s disease, is unclear.

For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using carbidopa and levodopa for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).

Information for Patients: The patient should be informed that this combination product is an immediate-release formulation of carbidopa and levodopa that is designed to begin release of ingredients within 30 minutes. It is important that carbidopa and levodopa be taken at regular intervals according to the schedule outlined by the physician. The patient should be cautioned not to change the prescribed dosage regimen and not to add any additional antiparkinson medications, including other carbidopa levodopa preparations, without first consulting the physician.

Patients should be advised that sometimes a 'wearing-off' effect may occur at the end of the dosing interval. The physician should be notified if such response poses a problem to lifestyle.

Patients should be advised that occasionally, dark color (red, brown, or black) may appear in saliva, urine, or sweat after ingestion of carbidopa and levodopa. Although the color appears to be clinically insignificant, garments may become discolored.

The patient should be advised that a change in diet to foods that are high in protein may delay the absorption of levodopa and may reduce the amount taken up in the circulation. Excessive acidity also delays stomach emptying, thus delaying the absorption of levodopa. Iron salts (such as in multivitamin tablets) may also reduce the amount of levodopa available to the body. The above factors may reduce the clinical effectiveness of the levodopa or carbidopa levodopa therapy.

Patients should be alerted to the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including levodopa. Patients should be advised to exercise caution while driving or operating machinery and that if they have experienced somnolence and/or sudden sleep onset, they must refrain from these activities. (See WARNINGS, Falling Asleep During Activities of Daily Living and Somnolence.)

There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson s disease, including carbidopa and levodopa. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with carbidopa and levodopa. Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges, or other intense urges while taking carbidopa and levodopa. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa (see PRECAUTIONS, Impulse Control/Compulsive Behaviors).

Laboratory Tests: Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen BUN and positive Coombs test have also been reported. Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of this combination product than with levodopa.

Carbidopa and levodopa may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. This reaction will not be altered by boiling the urine specimen. False-negative tests may result with the use of glucose-oxidase methods of testing for glucosuria.

Cases of falsely diagnosed pheochromocytoma in patients on carbidopa levodopa therapy have been reported very rarely. Caution should be exercised when interpreting the plasma and urine levels of catecholamines and their metabolites in patients on levodopa or carbidopa levodopa therapy.

Drug Interactions: Caution should be exercised when the following drugs are administered concomitantly with carbidopa and levodopa.

Symptomatic postural hypotension occurred when carbidopa and levodopa was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with carbidopa and levodopa is started, dosage adjustment of the antihypertensive drug may be required.

For patients receiving MAO inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline and carbidopa and levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa levodopa alone (see CONTRAINDICATIONS).

There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa and levodopa.

Dopamine D 2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with carbidopa and levodopa should be carefully observed for loss of therapeutic response.

Use of carbidopa and levodopa with dopamine-depleting agents (e.g., reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.

Carbidopa and levodopa and iron salts or multivitamins containing iron salts should be coadministered with caution. Iron salts can form chelates with levodopa and carbidopa and consequently reduce the bioavailability of carbidopa and levodopa.

Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also adversely affect disease control by its dopamine receptor antagonistic properties.

Carcinogenesis, Mutagenesis, Impairment of Fertility: In a two-year bioassay of carbidopa and levodopa, no evidence of carcinogenicity was found in rats receiving doses of approximately two times the maximum daily human dose of carbidopa and four times the maximum daily human dose of levodopa.

In reproduction studies with carbidopa and levodopa, no effects on fertility were found in rats receiving doses of approximately two times the maximum daily human dose of carbidopa and four times the maximum daily human dose of levodopa.

Pregnancy: Teratogenic Effects: Pregnancy Category C: No teratogenic effects were observed in a study in mice receiving up to 20 times the maximum recommended human dose of carbidopa and levodopa. There was a decrease in the number of live pups delivered by rats receiving approximately two times the maximum recommended human dose of carbidopa and approximately five times the maximum recommended human dose of levodopa during organogenesis. Carbidopa and levodopa caused both visceral and skeletal malformations in rabbits at all doses and ratios of carbidopa/levodopa tested, which ranged from 10 times/5 times the maximum recommended human dose of carbidopa/levodopa to 20 times/10 times the maximum recommended human dose of carbidopa/levodopa.

There are no adequate or well-controlled studies in pregnant women. It has been reported from individual cases that levodopa crosses the human placental barrier, enters the fetus, and is metabolized. Carbidopa concentrations in fetal tissue appeared to be minimal. Use of carbidopa and levodopa in women of childbearing potential requires that the anticipated benefits of the drug be weighed against possible hazards to mother and child.

Nursing Mothers: Levodopa has been detected in human milk. Caution should be exercised when carbidopa and levodopa is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Use of the drug in patients below the age of 18 is not recommended.

Geriatric Use: In the clinical efficacy trials for carbidopa and levodopa, almost half of the patients were older than 65, but few were older than 75. No overall meaningful differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals to adverse drug reactions such as hallucinations cannot be ruled out. There is no specific dosing recommendation based upon clinical pharmacology data as carbidopa and levodopa is titrated as tolerated for clinical effect.

Adverse Reactions ⮝

The most common adverse reactions reported with carbidopa and levodopa have included dyskinesias, such as choreiform, dystonic, and other involuntary movements, and nausea.

The following other adverse reactions have been reported with carbidopa and levodopa:

Body As A Whole: chest pain, asthenia.

Cardiovascular: cardiac irregularities, hypotension, orthostatic effects including orthostatic hypotension, hypertension, syncope, phlebitis, palpitation.

Gastrointestinal: dark saliva, gastrointestinal bleeding, development of duodenal ulcer, anorexia, vomiting, diarrhea, constipation, dyspepsia, dry mouth, taste alterations.

Hematologic: agranulocytosis, hemolytic and non-hemolytic anemia, thrombocytopenia, leukopenia.

Hypersensitivity: angioedema, urticaria, pruritus, Henoch-Sch nlein purpura, bullous lesions (including pemphigus-like reactions).

Musculoskeletal: back pain, shoulder pain, muscle cramps.

Nervous System/Psychiatric: psychotic episodes including delusions, hallucinations, and paranoid ideation, bradykinetic episodes ("on-off" phenomenon), confusion, agitation, dizziness, somnolence, dream abnormalities including nightmares, insomnia, paresthesia, headache, depression with or without development of suicidal tendencies, dementia, pathological gambling, increased libido including hypersexuality, impulse control symptoms. Convulsions also have occurred; however, a causal relationship with carbidopa and levodopa has not been established.

Respiratory: dyspnea, upper respiratory infection.

Skin: rash, increased sweating, alopecia, dark sweat.

Urogenital: urinary tract infection, urinary frequency, dark urine.

Laboratory Tests: decreased hemoglobin and hematocrit; abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), LDH, bilirubin, BUN, Coombs test; elevated serum glucose; white blood cells, bacteria, and blood in the urine.

Other adverse reactions that have been reported with levodopa alone and with various carbidopa levodopa formulations, and may occur with this combination product are:

Body As A Whole: abdominal pain and distress, fatigue.

Cardiovascular: myocardial infarction.

Gastrointestinal: gastrointestinal pain, dysphagia, sialorrhea, flatulence, bruxism, burning sensation of the tongue, heartburn, hiccups.

Metabolic: edema, weight gain, weight loss.

Musculoskeletal: leg pain.

Nervous System/Psychiatric: ataxia, extrapyramidal disorder, falling, anxiety, gait abnormalities, nervousness, decreased mental acuity, memory impairment, disorientation, euphoria, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), trismus, increased tremor, numbness, muscle twitching, activation of latent Horner's syndrome, peripheral neuropathy.

Respiratory: pharyngeal pain, cough.

Skin: malignant melanoma (see also CONTRAINDICATIONS), flushing.

Special Senses: oculogyric crises, diplopia, blurred vision, dilated pupils.

Urogenital: urinary retention, urinary incontinence, priapism.

Miscellaneous: bizarre breathing patterns, faintness, hoarseness, malaise, hot flashes, sense of stimulation.

Laboratory Tests: decreased white blood cell count and serum potassium; increased serum creatinine and uric acid; protein and glucose in urine.

To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

Overdosage ⮝

Management of acute overdosage with carbidopa and levodopa is the same as management of acute overdosage with levodopa. Pyridoxine is not effective in reversing the actions of this product.

General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered judiciously and an adequate airway maintained. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs as well as carbidopa and levodopa tablets should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known.

Based on studies in which high doses of levodopa and/or carbidopa were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1,500 to 2,000 mg/kg are expected to die. A significant proportion of infant rats of both sexes are expected to die at a dose of 800 mg/kg. A significant proportion of rats are expected to die after treatment with similar doses of carbidopa. The addition of carbidopa in a 1:10 ratio with levodopa increases the dose at which a significant proportion of mice are expected to die to 3,360 mg/kg.

Dosage And Administration ⮝

The optimum daily dosage of carbidopa and levodopa must be determined by careful titration in each patient. Carbidopa and levodopa tablets are available in a 1:4 ratio of carbidopa to levodopa (25 mg/100 mg) as well as 1:10 ratio (25 mg/250 mg and 10 mg/100 mg). Tablets of the two ratios may be given separately or combined as needed to provide the optimum dosage.

Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.

Usual Initial Dosage: Dosage is best initiated with one tablet of carbidopa and levodopa 25 mg/100 mg three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight tablets of carbidopa and levodopa 25 mg/100 mg a day is reached.

If carbidopa and levodopa 10 mg/100 mg is used, dosage may be initiated with one tablet three or four times a day. However, this will not provide an adequate amount of carbidopa for many patients. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (2 tablets four times a day) is reached.

How to Transfer Patients from Levodopa: Levodopa must be discontinued at least twelve hours before starting this combination product. A daily dosage of carbidopa and levodopa should be chosen that will provide approximately 25% of the previous levodopa dosage. Patients who are taking less than 1,500 mg of levodopa a day should be started on one tablet of carbidopa and levodopa 25 mg/100 mg three or four times a day. The suggested starting dosage for most patients taking more than 1,500 mg of levodopa is one tablet of carbidopa and levodopa 25 mg/250 mg three or four times a day.

Maintenance: Therapy should be individualized and adjusted according to the desired therapeutic response. At least 70 to 100 mg of carbidopa per day should be provided. When a greater proportion of carbidopa is required, one 25 mg/100 mg tablet may be substituted for each 10 mg/100 mg tablet. When more levodopa is required, each 25 mg/250 mg tablet should be substituted for a 25 mg/100 mg tablet or a 10 mg/100 mg tablet. If necessary, the dosage of carbidopa levodopa 25 mg/250 mg may be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day. Experience with total daily dosages of carbidopa greater than 200 mg is limited.

Because both therapeutic and adverse responses occur more rapidly with this combination product than with levodopa alone, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly with carbidopa and levodopa than with levodopa. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.

Addition of Other Antiparkinsonian Medications: Standard drugs for Parkinson's disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while carbidopa and levodopa is being administered, although dosage adjustments may be required.

Interruption of Therapy: Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa and levodopa. Patients should be observed carefully if abrupt reduction or discontinuation of carbidopa and levodopa is required, especially if the patient is receiving neuroleptics. (See WARNINGS.)

If general anesthesia is required, carbidopa and levodopa may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS, and the usual daily dosage may be administered as soon as the patient is able to take oral medication.

How Supplied ⮝

25 mg/100 mg Each yellow, mottled, round tablet imprinted with on one side and 539 and bisect on the other contains 25 mg of Carbidopa, USP and 100 mg of Levodopa, USP and is supplied in unit dose packages of 100 (10 x 10) NDC 68084-093-01.

25 mg/250 mg Each light blue, mottled, round tablet imprinted with on one side and 540 and bisect on the other contains 25 mg of Carbidopa, USP and 250 mg of Levodopa, USP and is supplied in unit dose packages of 100 (10 x 10) NDC 68084-094-01.

Store at 25 C (77 F); excursions permitted to 15 to 30 C (59 to 86 F) [See USP Controlled Room Temperature].

Protect from light.

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

Carbidopa And Levodopa Tablet ⮝

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:65084-107(NDC:51862-855) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 10 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength Magnesium Stearate (UNII: 70097M6I30) Microcrystalline Cellulose (UNII: OP1R32D61U) Starch, Corn (UNII: O8232NY3SJ) FD&C Blue No. 2 (UNII: L06K8R7DQK)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code m;711 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:65084-107-10 10 in 1 BOX 04/15/2019 09/17/2019 1 10 in 1 BLISTER PACK; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073618 07/16/2018 09/17/2019

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:65084-108(NDC:51862-856) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength Magnesium Stearate (UNII: 70097M6I30) Microcrystalline Cellulose (UNII: OP1R32D61U) Starch, Corn (UNII: O8232NY3SJ) D&C Yellow No. 10 (UNII: 35SW5USQ3G) FD&C Yellow No. 6 (UNII: H77VEI93A8)

Product Characteristics Color YELLOW (mottled-yellow) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code m;721 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:65084-108-10 10 in 1 BOX 10/01/2019 1 10 in 1 BLISTER PACK; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073589 07/16/2018

Labeler - McKesson Corporation dba RX Pak (025183281)

Establishment
Name	Address	ID/FEI	Business Operations
McKesson Corporation dba RX Pak		025183281	RELABEL(65084-108, 65084-107) , REPACK(65084-107, 65084-108)

Revised: 10/2019 Document Id: e13d80c4-4005-442e-b29a-2d3ba80a6089 34391-3 Set id: b07f7826-2383-4932-964b-03395c0e8af2 Version: 7 Effective Time: 20191004 McKesson Corporation dba RX Pak

Package/label Display Panel 25mg/250mg ⮝

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0615-8010(NDC:0093-0293) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8) ALUMINUM OXIDE (UNII: LMI26O6933)

Product Characteristics Color YELLOW (mottled-yellow) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code 93;293;TEVA Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0615-8010-05 15 in 1 BLISTER PACK; Type 0: Not a Combination Product 04/01/1993 2 NDC:0615-8010-39 30 in 1 BLISTER PACK; Type 0: Not a Combination Product 04/01/1993

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073589 04/01/1993

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0615-8011(NDC:0093-0294) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 250 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) ALUMINUM OXIDE (UNII: LMI26O6933)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code 93;294 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0615-8011-39 30 in 1 BLISTER PACK; Type 0: Not a Combination Product 01/01/1993

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073607 01/01/1993

Labeler - NCS HealthCare of KY, Inc dba Vangard Labs (050052943)

Establishment
Name	Address	ID/FEI	Business Operations
NCS HealthCare of KY, Inc dba Vangard Labs		050052943	RELABEL(0615-8010, 0615-8011) , REPACK(0615-8010, 0615-8011)

Revised: 5/2016 Document Id: 9cf5c2a0-7641-4fc7-952d-3e003cc8519f 34391-3 Set id: 3eb542bf-be07-4fd4-9083-dd8da08368fd Version: 2 Effective Time: 20160520 NCS HealthCare of KY, Inc dba Vangard Labs

Description  ⮝

Carbidopa and levodopa is a combination product for the treatment of Parkinson's disease and syndrome.

Carbidopa, USP an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.25. It is designated chemically as (-)-L- -hydrazino- -methyl- -(3,4-dihydroxybenzene) propanoic acid monohydrate. Its molecular formula is C10H14N2O4.H2O, and its structural formula is:

Tablet content is expressed in terms of anhydrous carbidopa which has a molecular weight of 226.23.

Levodopa, USP an aromatic amino acid, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 197.19. It is designated chemically as (-)-L- -amino- -(3,4-dihydroxybenzene) propanoic acid. Its molecular formula is C9H11NO4, and its structural formula is:

Carbidopa and levodopa tablets, USP for oral administration, are supplied in three strengths:

10 mg/100 mg, containing 10 mg of carbidopa and 100 mg of levodopa.

25 mg/100 mg, containing 25 mg of carbidopa and 100 mg of levodopa.

25 mg/250 mg, containing 25 mg of carbidopa and 250 mg of levodopa.

In addition, each tablet contains the following inactive ingredients:

10 mg/100 mg Corn starch, FD&C blue #2 aluminum lake, magnesium stearate, microcrystalline cellulose, and pregelatinized starch (maize).

25 mg/100 mg Corn starch, D&C yellow #10 aluminum lake, FD&C yellow #6 aluminum lake (sunset yellow lake), magnesium stearate, microcrystalline cellulose, and pregelatinized starch (maize).

25 mg/250 mg Corn starch, FD&C blue #2 aluminum lake, magnesium stearate, microcrystalline cellulose, and pregelatinized starch (maize).

Clinical Pharmacology  ⮝

Mechanism of Action: Parkinson's disease is a progressive, neurodegenerative disorder of the extrapyramidal nervous system affecting the mobility and control of the skeletal muscular system. Its characteristic features include resting tremor, rigidity, and bradykinetic movements. Symptomatic treatments, such as levodopa therapies, may permit the patient better mobility.

Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier. However, levodopa, 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.

Pharmacodynamics: 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. For this reason, large doses of levodopa are required for adequate therapeutic effect, and these may often be accompanied by nausea and other adverse reactions, some of which are attributable to dopamine formed in extracerebral tissues.

Since levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be impaired in some patients on a high protein diet.

Carbidopa inhibits decarboxylation of peripheral levodopa. It does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system.

The incidence of levodopa-induced nausea and vomiting is less with the combination product than with levodopa. In many patients, this reduction in nausea and vomiting will permit more rapid dosage titration.

Since its decarboxylase inhibiting activity is limited to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available for transport to the brain.

Pharmacokinetics: Carbidopa reduces the amount of levodopa required to produce a given response by about 75% and, when administered with levodopa, increases both plasma levels and the plasma half-life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid.

The plasma half-life of levodopa is about 50 minutes, without carbidopa. When carbidopa and levodopa are administered together, the half-life of levodopa is increased to about 1.5 hours. At steady state, the bioavailability of carbidopa from carbidopa and levodopa tablets is approximately 99% relative to the concomitant administration of carbidopa and levodopa.

In clinical pharmacologic studies, simultaneous administration of carbidopa and levodopa produced greater urinary excretion of levodopa in proportion to the excretion of dopamine than administration of the two drugs at separate times.

Pyridoxine hydrochloride (vitamin B6), in oral doses of 10 mg to 25 mg, may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine; therefore, carbidopa and levodopa can be given to patients receiving supplemental pyridoxine (vitamin B6).

Special Populations
Geriatric: A study in eight young healthy subjects (21 to 22 yr) and eight elderly healthy subjects (69 to 76 yr) showed that the absolute bioavailability of levodopa was similar between young and elderly subjects following oral administration of levodopa and carbidopa. However, the systemic exposure (AUC) of levodopa was increased by 55% in elderly subjects compared to young subjects. Based on another study in forty patients with Parkinson s disease, there was a correlation between age of patients and the increase of AUC of levodopa following administration of levodopa and an inhibitor of peripheral dopa decarboxylase. AUC of levodopa was increased by 28% in elderly patients (greater than or equal to 65 yr) compared to young patients (less than 65 yr). Additionally, mean value of Cmax for levodopa was increased by 24% in elderly patients (greater than or equal to 65 yr) compared to young patients (less than 65 yr) (see PRECAUTIONS, Geriatric Use).

The AUC of carbidopa was increased in elderly subjects (n=10, 65 to 76 yr) by 29% compared to young subjects (n=24, 23 to 64 yr) following IV administration of 50 mg levodopa with carbidopa (50 mg). This increase is not considered a clinically significant impact.

Indications And Usage  ⮝

Carbidopa and levodopa tablets, USP are indicated in the treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism that may follow carbon monoxide intoxication or manganese intoxication.

Carbidopa allows patients treated for Parkinson's disease to use much lower doses of levodopa. Some patients who responded poorly to levodopa have improved on carbidopa and levodopa. This is most likely due to decreased peripheral decarboxylation of levodopa caused by administration of carbidopa rather than by a primary effect of carbidopa on the nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa.

Carbidopa may also reduce nausea and vomiting and permit more rapid titration of levodopa.

Contraindications  ⮝

Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with carbidopa and levodopa. These inhibitors must be discontinued at least two weeks prior to initiating therapy with this combination product. Carbidopa and levodopa may be administered concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl) (see PRECAUTIONS, Drug Interactions).

Carbidopa and levodopa is contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma.

Warnings  ⮝

When carbidopa and levodopa tablets are to be given to patients who are being treated with levodopa, levodopa must be discontinued at least twelve hours before therapy with the combination product is started. In order to reduce adverse reactions, it is necessary to individualize therapy. See DOSAGE AND ADMINISTRATION section before initiating therapy.

The addition of carbidopa with levodopa in the form of this combination product reduces the peripheral effects (nausea, vomiting) due to decarboxylation of levodopa; however, carbidopa does not decrease the adverse reactions due to the central effects of levodopa. Because carbidopa permits more levodopa to reach the brain and more dopamine to be formed, certain adverse central nervous system (CNS) effects, e.g., dyskinesias (involuntary movements), may occur at lower dosages and sooner with carbidopa and levodopa than with levodopa alone.

All patients should be observed carefully for the development of depression with concomitant suicidal tendencies.

Carbidopa and levodopa should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.

As with levodopa, care should be exercised in administering the combination product, to patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias. In such patients, cardiac function should be monitored with particular care during the period of initial dosage adjustment, in a facility with provisions for intensive cardiac care.

As with levodopa, treatment with the combination product may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer.

Falling Asleep During Activities of Daily Living and Somnolence

Patients taking carbidopa and levodopa alone or with other dopaminergic drugs have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (includes operation of motor vehicles). Road traffic accidents attributed to sudden sleep onset have been reported. Although many patients reported somnolence while on dopaminergic medications, there have been reports of road traffic accidents attributed to sudden onset of sleep in which the patient did not perceive any warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Sudden onset of sleep has been reported to occur as long as one year after the initiation of treatment.

Falling asleep while engaged in activities of daily living usually occurs in patients experiencing preexisting somnolence, although some patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribers should be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Patients should be advised to exercise caution while driving or operating machines during treatment with carbidopa and levodopa. Patients who have already experienced somnolence or an episode of sudden sleep onset should not participate in these activities during treatment with carbidopa and levodopa.

Before initiating treatment with carbidopa and levodopa, advise patients about the potential to develop drowsiness and ask specifically about factors that may increase the risk for somnolence with carbidopa and levodopa such as the use of concomitant sedating medications and the presence of sleep disorders. Consider discontinuing carbidopa and levodopa in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.). If treatment with carbidopa and levodopa continues, patients should be advised not to drive and to avoid other potentially dangerous activities that might result in harm if the patients become somnolent. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

Hyperpyrexia and Confusion

Hyperpyrexia and Confusion

Sporadic cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) have been reported in association with dose reductions or withdrawal of certain antiparkinsonian agents such as levodopa, carbidopa levodopa, or carbidopa levodopa extended release. Therefore, patients should be observed carefully when the dosage of levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.

NMS is an uncommon but life-threatening syndrome characterized by fever or hyperthermia. Neurological findings, including muscle rigidity, involuntary movements, altered consciousness, mental status changes; other disturbances, such as autonomic dysfunction, tachycardia, tachypnea, sweating, hyper-or hypotension; laboratory findings, such as creatine phosphokinase elevation, leukocytosis, myoglobinuria, and increased serum myoglobin have been reported.

The early diagnosis of this condition is important for the appropriate management of these patients. Considering NMS as a possible diagnosis and ruling out other acute illnesses (e.g., pneumonia, systemic infection, etc.) is essential. This may be especially complex if the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology.

The management of NMS should include: 1) intensive symptomatic treatment and medical monitoring and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene, are often used in the treatment of NMS; however, their effectiveness has not been demonstrated in controlled studies.

Precautions  ⮝

General: As with levodopa, periodic evaluations of hepatic, hematopoietic, cardiovascular, and renal function are recommended during extended therapy.

Patients with chronic wide-angle glaucoma may be treated cautiously with carbidopa and levodopa provided the intraocular pressure is well-controlled and the patient is monitored carefully for changes in intraocular pressure during therapy.

Dyskinesia: Levodopa alone, as well as carbidopa and levodopa, is associated with dyskinesias. The occurrence of dyskinesias may require dosage reduction.

Hallucinations/Psychotic-Like Behavior: Hallucinations and psychotic-like behavior have been reported with dopaminergic medications. In general, hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa. Hallucinations may be accompanied by confusion and to a lesser extent sleep disorder (insomnia) and excessive dreaming.

Carbidopa and levodopa may have similar effects on thinking and behavior. This abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.

Ordinarily, patients with a major psychotic disorder should not be treated with carbidopa and levodopa, because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson s disease and may decrease the effectiveness of carbidopa and levodopa.

Impulse Control/Compulsive Behaviors: Reports of patients taking dopaminergic medications (medications that increase central dopaminergic tone), suggest that patients may experience an intense urge to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or the caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with carbidopa and levodopa. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa (see Information for Patients).

Melanoma: Epidemiological studies have shown that patients with Parkinson s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson s disease or other factors, such as drugs used to treat Parkinson s disease, is unclear.

For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using carbidopa and levodopa for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).

Information for Patients: The patient should be informed that this combination product is an immediate-release formulation of carbidopa and levodopa that is designed to begin release of ingredients within 30 minutes. It is important that carbidopa and levodopa be taken at regular intervals according to the schedule outlined by the physician. The patient should be cautioned not to change the prescribed dosage regimen and not to add any additional antiparkinson medications, including other carbidopa levodopa preparations, without first consulting the physician.

Patients should be advised that sometimes a 'wearing-off' effect may occur at the end of the dosing interval. The physician should be notified if such response poses a problem to lifestyle.

Patients should be advised that occasionally, dark color (red, brown, or black) may appear in saliva, urine, or sweat after ingestion of carbidopa and levodopa. Although the color appears to be clinically insignificant, garments may become discolored.

The patient should be advised that a change in diet to foods that are high in protein may delay the absorption of levodopa and may reduce the amount taken up in the circulation. Excessive acidity also delays stomach emptying, thus delaying the absorption of levodopa. Iron salts (such as in multivitamin tablets) may also reduce the amount of levodopa available to the body. The above factors may reduce the clinical effectiveness of the levodopa or carbidopa levodopa therapy.

Patients should be alerted to the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including levodopa. Patients should be advised to exercise caution while driving or operating machinery and that if they have experienced somnolence and/or sudden sleep onset, they must refrain from these activities. (See WARNINGS, Falling Asleep During Activities of Daily Living and Somnolence.)

There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson s disease, including carbidopa and levodopa. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with carbidopa and levodopa. Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges, or other intense urges while taking carbidopa and levodopa. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking carbidopa and levodopa (see PRECAUTIONS, Impulse Control/Compulsive Behaviors).

Laboratory Tests: Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, SGOT (AST), SGPT (ALT), lactic dehydrogenase (LDH), and bilirubin. Abnormalities in blood urea nitrogen BUN and positive Coombs test have also been reported. Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of this combination product than with levodopa.

Carbidopa and levodopa may cause a false-positive reaction for urinary ketone bodies when a test tape is used for determination of ketonuria. This reaction will not be altered by boiling the urine specimen. False-negative tests may result with the use of glucose-oxidase methods of testing for glucosuria.

Cases of falsely diagnosed pheochromocytoma in patients on carbidopa levodopa therapy have been reported very rarely. Caution should be exercised when interpreting the plasma and urine levels of catecholamines and their metabolites in patients on levodopa or carbidopa levodopa therapy.

Drug Interactions: Caution should be exercised when the following drugs are administered concomitantly with carbidopa and levodopa.

Symptomatic postural hypotension occurred when carbidopa and levodopa was added to the treatment of a patient receiving antihypertensive drugs. Therefore, when therapy with carbidopa and levodopa is started, dosage adjustment of the antihypertensive drug may be required.

For patients receiving MAO inhibitors (Type A or B), see CONTRAINDICATIONS. Concomitant therapy with selegiline and carbidopa and levodopa may be associated with severe orthostatic hypotension not attributable to carbidopa levodopa alone (see CONTRAINDICATIONS).

There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa and levodopa.

Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these drugs with carbidopa and levodopa should be carefully observed for loss of therapeutic response.

Use of carbidopa and levodopa with dopamine-depleting agents (e.g., reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.

Carbidopa and levodopa and iron salts or multivitamins containing iron salts should be coadministered with caution. Iron salts can form chelates with levodopa and carbidopa and consequently reduce the bioavailability of carbidopa and levodopa.

Although metoclopramide may increase the bioavailability of levodopa by increasing gastric emptying, metoclopramide may also adversely affect disease control by its dopamine receptor antagonistic properties.

Carcinogenesis, Mutagenesis, Impairment of Fertility: In a two-year bioassay of carbidopa and levodopa, no evidence of carcinogenicity was found in rats receiving doses of approximately two times the maximum daily human dose of carbidopa and four times the maximum daily human dose of levodopa.

In reproduction studies with carbidopa and levodopa, no effects on fertility were found in rats receiving doses of approximately two times the maximum daily human dose of carbidopa and four times the maximum daily human dose of levodopa.

Pregnancy: Teratogenic Effects: Pregnancy Category C: No teratogenic effects were observed in a study in mice receiving up to 20 times the maximum recommended human dose of carbidopa and levodopa. There was a decrease in the number of live pups delivered by rats receiving approximately two times the maximum recommended human dose of carbidopa and approximately five times the maximum recommended human dose of levodopa during organogenesis. Carbidopa and levodopa caused both visceral and skeletal malformations in rabbits at all doses and ratios of carbidopa/levodopa tested, which ranged from 10 times/5 times the maximum recommended human dose of carbidopa/levodopa to 20 times/10 times the maximum recommended human dose of carbidopa/levodopa.

There are no adequate or well-controlled studies in pregnant women. It has been reported from individual cases that levodopa crosses the human placental barrier, enters the fetus, and is metabolized. Carbidopa concentrations in fetal tissue appeared to be minimal. Use of carbidopa and levodopa in women of childbearing potential requires that the anticipated benefits of the drug be weighed against possible hazards to mother and child.

Nursing Mothers: Levodopa has been detected in human milk. Caution should be exercised when carbidopa and levodopa is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Use of the drug in patients below the age of 18 is not recommended.

Geriatric Use: In the clinical efficacy trials for carbidopa and levodopa, almost half of the patients were older than 65, but few were older than 75. No overall meaningful differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals to adverse drug reactions such as hallucinations cannot be ruled out. There is no specific dosing recommendation based upon clinical pharmacology data as carbidopa and levodopa is titrated as tolerated for clinical effect.

Adverse Reactions  ⮝

The most common adverse reactions reported with carbidopa and levodopa have included dyskinesias, such as choreiform, dystonic, and other involuntary movements, and nausea.

The following other adverse reactions have been reported with carbidopa and levodopa:

Body As A Whole: chest pain, asthenia.

Cardiovascular: cardiac irregularities, hypotension, orthostatic effects including orthostatic hypotension, hypertension, syncope, phlebitis, palpitation.

Gastrointestinal: dark saliva, gastrointestinal bleeding, development of duodenal ulcer, anorexia, vomiting, diarrhea, constipation, dyspepsia, dry mouth, taste alterations.

Hematologic: agranulocytosis, hemolytic and non-hemolytic anemia, thrombocytopenia, leukopenia.

Hypersensitivity: angioedema, urticaria, pruritus, Henoch-Sch nlein purpura, bullous lesions (including pemphigus-like reactions).

Musculoskeletal: back pain, shoulder pain, muscle cramps.

Nervous System/Psychiatric: psychotic episodes including delusions, hallucinations, and paranoid ideation, bradykinetic episodes ("on-off" phenomenon), confusion, agitation, dizziness, somnolence, dream abnormalities including nightmares, insomnia, paresthesia, headache, depression with or without development of suicidal tendencies, dementia, pathological gambling, increased libido including hypersexuality, impulse control symptoms. Convulsions also have occurred; however, a causal relationship with carbidopa and levodopa has not been established.

Respiratory: dyspnea, upper respiratory infection.

Skin: rash, increased sweating, alopecia, dark sweat.

Urogenital: urinary tract infection, urinary frequency, dark urine.

Laboratory Tests: decreased hemoglobin and hematocrit; abnormalities in alkaline phosphatase, SGOT (AST), SGPT (ALT), LDH, bilirubin, BUN, Coombs test; elevated serum glucose; white blood cells, bacteria, and blood in the urine.

Other adverse reactions that have been reported with levodopa alone and with various carbidopa levodopa formulations, and may occur with this combination product are:

Body As A Whole: abdominal pain and distress, fatigue.

Cardiovascular: myocardial infarction.

Gastrointestinal: gastrointestinal pain, dysphagia, sialorrhea, flatulence, bruxism, burning sensation of the tongue, heartburn, hiccups.

Metabolic: edema, weight gain, weight loss.

Musculoskeletal: leg pain.

Nervous System/Psychiatric: ataxia, extrapyramidal disorder, falling, anxiety, gait abnormalities, nervousness, decreased mental acuity, memory impairment, disorientation, euphoria, blepharospasm (which may be taken as an early sign of excess dosage; consideration of dosage reduction may be made at this time), trismus, increased tremor, numbness, muscle twitching, activation of latent Horner's syndrome, peripheral neuropathy.

Respiratory: pharyngeal pain, cough.

Skin: malignant melanoma (see also CONTRAINDICATIONS), flushing.

Special Senses: oculogyric crises, diplopia, blurred vision, dilated pupils.

Urogenital: urinary retention, urinary incontinence, priapism.

Miscellaneous: bizarre breathing patterns, faintness, hoarseness, malaise, hot flashes, sense of stimulation.

Laboratory Tests: decreased white blood cell count and serum potassium; increased serum creatinine and uric acid; protein and glucose in urine.

To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

Overdosage  ⮝

Management of acute overdosage with carbidopa and levodopa is the same as management of acute overdosage with levodopa. Pyridoxine is not effective in reversing the actions of this product.

General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered judiciously and an adequate airway maintained. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs as well as carbidopa and levodopa tablets should be taken into consideration. To date, no experience has been reported with dialysis; hence, its value in overdosage is not known.

Based on studies in which high doses of levodopa and/or carbidopa were administered, a significant proportion of rats and mice given single oral doses of levodopa of approximately 1,500 to 2,000 mg/kg are expected to die. A significant proportion of infant rats of both sexes are expected to die at a dose of 800 mg/kg. A significant proportion of rats are expected to die after treatment with similar doses of carbidopa. The addition of carbidopa in a 1:10 ratio with levodopa increases the dose at which a significant proportion of mice are expected to die to 3,360 mg/kg.

Dosage And Administration  ⮝

The optimum daily dosage of carbidopa and levodopa must be determined by careful titration in each patient. Carbidopa and levodopa tablets are available in a 1:4 ratio of carbidopa to levodopa (25 mg/100 mg) as well as 1:10 ratio (25 mg/250 mg and 10 mg/100 mg). Tablets of the two ratios may be given separately or combined as needed to provide the optimum dosage.

Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.

Usual Initial Dosage: Dosage is best initiated with one tablet of carbidopa and levodopa

25 mg/100 mg three times a day. This dosage schedule provides 75 mg of carbidopa per day. Dosage may be increased by one tablet every day or every other day, as necessary, until a dosage of eight tablets of carbidopa and levodopa 25 mg/100 mg a day is reached.

If carbidopa and levodopa 10 mg/100 mg is used, dosage may be initiated with one tablet three or four times a day. However, this will not provide an adequate amount of carbidopa for many patients. Dosage may be increased by one tablet every day or every other day until a total of eight tablets (2 tablets four times a day) is reached.

How to Transfer Patients from Levodopa: Levodopa must be discontinued at least twelve hours before starting this combination product. A daily dosage of carbidopa and levodopa should be chosen that will provide approximately 25% of the previous levodopa dosage. Patients who are taking less than 1,500 mg of levodopa a day should be started on one tablet of carbidopa and levodopa 25 mg/100 mg three or four times a day. The suggested starting dosage for most patients taking more than 1,500 mg of levodopa is one tablet of carbidopa and levodopa 25 mg/250 mg three or four times a day.

Maintenance: Therapy should be individualized and adjusted according to the desired therapeutic response. At least 70 to 100 mg of carbidopa per day should be provided. When a greater proportion of carbidopa is required, one 25 mg/100 mg tablet may be substituted for each 10 mg/100 mg tablet. When more levodopa is required, each 25 mg/250 mg tablet should be substituted for a 25 mg/100 mg tablet or a 10 mg/100 mg tablet. If necessary, the dosage of carbidopa levodopa 25 mg/250 mg may be increased by one-half or one tablet every day or every other day to a maximum of eight tablets a day. Experience with total daily dosages of carbidopa greater than 200 mg is limited.

Because both therapeutic and adverse responses occur more rapidly with this combination product than with levodopa alone, patients should be monitored closely during the dose adjustment period. Specifically, involuntary movements will occur more rapidly with carbidopa and levodopa than with levodopa. The occurrence of involuntary movements may require dosage reduction. Blepharospasm may be a useful early sign of excess dosage in some patients.

Addition of Other Antiparkinsonian Medications: Standard drugs for Parkinson's disease, other than levodopa without a decarboxylase inhibitor, may be used concomitantly while carbidopa and levodopa is being administered, although dosage adjustments may be required.

Interruption of Therapy: Sporadic cases of hyperpyrexia and confusion have been associated with dose reductions and withdrawal of carbidopa and levodopa. Patients should be observed carefully if abrupt reduction or discontinuation of carbidopa and levodopa is required, especially if the patient is receiving neuroleptics. (See WARNINGS.)

If general anesthesia is required, carbidopa and levodopa may be continued as long as the patient is permitted to take fluids and medication by mouth. If therapy is interrupted temporarily, the patient should be observed for symptoms resembling NMS, and the usual daily dosage may be administered as soon as the patient is able to take oral medication.

How Supplied  ⮝

Carbidopa and Levodopa Tablets, USP are supplied as follows:

10 mg/100 mg Each dark blue, mottled, round tablet imprinted with on one side and 538 and bisect on the other contains 10 mg of Carbidopa, USP and 100 mg of Levodopa, USP and is supplied in bottles of 100 (NDC 0228-2538-10) and 500 (NDC 0228-2538-50).

25 mg/100 mg Each yellow, mottled, round tablet imprinted with on one side and 539 and bisect on the other contains 25 mg of Carbidopa, USP and 100 mg of Levodopa, USP and is supplied in bottles of 100 (NDC 0228-2539-10), 500 (NDC 0228-2539-50) and 1,000 (NDC 0228-2539-96).

25 mg/250 mg Each light blue, mottled, round tablet imprinted with on one side and 540 and bisect on the other contains 25 mg of Carbidopa, USP and 250 mg of Levodopa, USP and is supplied in bottles of 100 (NDC 0228-2540-10), 500 (NDC 0228-2540-50) and 1,000 (NDC 0228-2540-96).

Store at 25 C (77 F); excursions permitted to 15 to 30 C (59 to 86 F) [See USP Controlled Room Temperature].

Protect from light.

Dispense in a well-closed, light-resistant container as defined in the USP.

Manufactured by:
Actavis Elizabeth LLC
Elizabeth, NJ 07207 USA

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA

40-9182

Revised February 2016

Package/label Display Panel  ⮝

NDC 60429-154-01

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:60429-152(NDC:0228-2538) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 10 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)

Product Characteristics Color blue (dark blue, mottled) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code R;538 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:60429-152-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 10/18/2013

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 10/18/2013

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:60429-153(NDC:0228-2539) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)

Product Characteristics Color yellow (mottled) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code R;539 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:60429-153-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 10/18/2013 2 NDC:60429-153-10 1000 in 1 BOTTLE; Type 0: Not a Combination Product 10/18/2013

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 10/18/2013

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:60429-154(NDC:0228-2540) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 250 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)

Product Characteristics Color blue (light blue, mottled) Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code R;540 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:60429-154-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 10/18/2013 2 NDC:60429-154-05 500 in 1 BOTTLE; Type 0: Not a Combination Product 10/18/2013

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 10/18/2013

Labeler - Golden State Medical Supply, Inc. (603184490)

Establishment
Name	Address	ID/FEI	Business Operations
Golden State Medical Supply, Inc.		603184490	repack(60429-152, 60429-153, 60429-154) , relabel(60429-152, 60429-153, 60429-154)

Revised: 11/2018 Document Id: 79b2ddee-982e-4481-e053-2991aa0aef12 34391-3 Set id: f1d6c0c3-6bff-4ea2-bcf8-0d679b5ccc6d Version: 3 Effective Time: 20181102 Golden State Medical Supply, Inc.

Repackaging Information ⮝

Please reference the How Supplied section listed above for a description of individual tablets. This drug product has been received by Aphena Pharma - TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below:

Count	25mg / 100 mg
90	71610-269-60
180	71610-269-80

Store between 20 -25 C (68 -77 F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children.

Repackaged by:

Cookeville, TN 38506

20190508JH

Principal Display Panel - 25/100mg ⮝

NDC 43353-510 - Carbidopa/Levodopa 25/100mg - Rx Only

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:43353-510(NDC:0228-2539) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8) MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)

Product Characteristics Color YELLOW (mottled) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code 539 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:43353-510-60 90 in 1 BOTTLE, PLASTIC 2 NDC:43353-510-80 180 in 1 BOTTLE, PLASTIC

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 09/01/1993

Labeler - Aphena Pharma Solutions - Tennessee, Inc. (128385585)

Establishment
Name	Address	ID/FEI	Business Operations
Aphena Pharma Solutions - Tennessee, Inc.		128385585	Repack(43353-510)

Revised: 7/2012 Document Id: 0b579053-078d-424a-ba43-56db5dcb90aa 34391-3 Set id: 8f03374a-70a1-45e8-83e7-ee0f3f0541a1 Version: 1 Effective Time: 20120717 Aphena Pharma Solutions - Tennessee, Inc.

No Title 1572452792 ⮝

40-9182

Revised February 2016

Rx Only

Carbidopa And Levodopa ⮝

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50090-3419(NDC:0228-2539) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)

Product Characteristics Color YELLOW (mottled) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code R;539 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50090-3419-1 90 in 1 BOTTLE; Type 0: Not a Combination Product 03/26/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 09/01/1993

Labeler - A-S Medication Solutions (830016429)

Establishment
Name	Address	ID/FEI	Business Operations
A-S Medication Solutions		830016429	RELABEL(50090-3419) , REPACK(50090-3419)

Revised: 10/2019 Document Id: fd974535-e2ee-4558-b897-cd54be5e7daa 34391-3 Set id: bce46b86-5ad8-4375-b04d-b25ce488ae29 Version: 3 Effective Time: 20191016 A-S Medication Solutions

No Title 1572452810 ⮝

40-8774

Revised January 2010

Rx Only

No Title 1572453334 ⮝

40-9182

Revised February 2016

Rx Only

Package Label.principal Display Panel  ⮝

NDC 0228-2538-10

Carbidopa and Levodopa Tablets, USP

10 mg/ 100 mg

Actavis

100 Tablets

Rx Only

Package Label.principal Display Panel ⮝

NDC 0228-2540-10

Carbidopa and Levodopa Tablets, USP

25 mg/ 250 mg

Actavis

100 Tablets

Rx Only

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0228-2538 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 10 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)

Product Characteristics Color BLUE (dark blue, mottled) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code R;538 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0228-2538-10 100 in 1 BOTTLE; Type 0: Not a Combination Product 09/01/1993 2 NDC:0228-2538-50 500 in 1 BOTTLE; Type 0: Not a Combination Product 09/01/1993

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 09/01/1993

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0228-2539 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8) MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)

Product Characteristics Color YELLOW (mottled) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code R;539 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0228-2539-10 100 in 1 BOTTLE; Type 0: Not a Combination Product 09/01/1993 2 NDC:0228-2539-50 500 in 1 BOTTLE; Type 0: Not a Combination Product 09/01/1993 3 NDC:0228-2539-96 1000 in 1 BOTTLE; Type 0: Not a Combination Product 09/01/1993

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 09/01/1993

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0228-2540 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 250 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)

Product Characteristics Color BLUE (light blue, mottled) Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code R;540 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0228-2540-10 100 in 1 BOTTLE; Type 0: Not a Combination Product 09/01/1993 2 NDC:0228-2540-50 500 in 1 BOTTLE; Type 0: Not a Combination Product 09/01/1993 3 NDC:0228-2540-96 1000 in 1 BOTTLE; Type 0: Not a Combination Product 09/01/1993

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 09/01/1993

Labeler - Actavis Pharma, Inc. (119723554)

Revised: 2/2016 Document Id: 553117b7-29a5-4c52-81eb-9b6a4e39b5c5 34391-3 Set id: a355d5f2-407d-40fa-a374-b3632261ea4a Version: 10 Effective Time: 20160216 Actavis Pharma, Inc.

Principal Display Panel - 25mg / 100mg ⮝

NDC 71610-269 - Carbidopa and Levodopa, USP 25 mg / 100 mg Tablets - Rx Only

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:71610-269(NDC:51407-167) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8)

Product Characteristics Color yellow (mottled-yellow) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code m;721 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:71610-269-60 90 in 1 BOTTLE; Type 0: Not a Combination Product 05/01/2019 2 NDC:71610-269-80 180 in 1 BOTTLE; Type 0: Not a Combination Product 05/01/2019

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073589 07/16/2018

Labeler - Aphena Pharma Solutions - Tennessee, LLC (128385585)

Establishment
Name	Address	ID/FEI	Business Operations
Aphena Pharma Solutions - Tennessee, LLC		128385585	REPACK(71610-269)

Revised: 5/2019 Document Id: a51379dd-c47a-4fcd-aed0-5f19c18bf12c 34391-3 Set id: eddc3e61-4fb3-4a2f-9102-406c5f397a64 Version: 1 Effective Time: 20190508 Aphena Pharma Solutions - Tennessee, LLC

No Title 1572456620 ⮝

40-9267

Revised January 2016

Rx Only

Packaging Information ⮝

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Actavis Parma, Inc. as follows:

(25 mg/100 mg / 100 UD) NDC 68084-093-01 packaged from NDC 0228-2539
(25 mg/250 mg / 100 UD) NDC 68084-094-01 packaged from NDC 0228-2540

Distributed by:
American Health Packaging
Columbus, OH 43217
8009201/1016

Package/label Display Panel Carton - 25 Mg/100 Mg ⮝

NDC 68084- 093-01

Carbidopa
and Levodopa
Tablets, USP
25 mg/100 mg

100 Tablets (10 x 10) Rx Only

Each Tablet Contains:
Carbidopa, USP............................................................................25 mg*
*(Anhydrous equivalent)
Levodopa, USP ............................................................................100 mg
Contains FD&C Yellow #6 Aluminum Lake (Sunset Yellow Lake) as a
color additive.

Usual Adult Dosage: See package insert for full prescribing
information.

Store at 20 to 25 C (68 to 77 F); excursions permitted between 15
to 30 C (59 to 86 F) [see USP Controlled Room Temperature]. Protect
from light.

Keep this and all drugs out of reach of children.

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

The drug product contained in this package is from
NDC # 0228-2539, Actavis Pharma, Inc.

Packaged and Distributed by:
American Health Packaging
Columbus, Ohio 43217

092713
0209301/0219

Package/label Display Panel Blister - 25 Mg/100 Mg ⮝

Carbidopa and Levodopa
Tablet, USP
25 mg/100 mg

Package/label Display Panel Carton - 25 Mg/250 Mg ⮝

NDC 68084- 094-01

Carbidopa
and Levodopa
Tablets, USP
25 mg/250 mg

100 Tablets (10 x 10) Rx Only

Each Tablet Contains:
Carbidopa, USP .................................................................. 25 mg*
*(Anhydrous equivalent)
Levodopa, USP....................................................................250 mg

Usual Adult Dosage: See package insert for full prescribing
information.

Store at 20 to 25 C (68 to 77 F); excursions permitted
between 15 to 30 C (59 to 86 F) [see USP Controlled Room
Temperature]. Protect from light.

Keep this and all drugs out of reach of children.

FOR YOUR PROTECTION: Do not use if blister is torn or
broken.

The drug product contained in this package is from
NDC # 0228-2540, Actavis Pharma, Inc.

Packaged and Distributed by:
American Health Packaging
Columbus, Ohio 43217

093338
0209401/0119

Package/label Display Panel Blister - 25 Mg/250 Mg ⮝

Carbidopa and Levodopa
Tablet, USP
25 mg/250 mg

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68084-093(NDC:0228-2539) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)

Product Characteristics Color yellow (mottled) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code R;539 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:68084-093-01 100 in 1 BOX, UNIT-DOSE 07/12/2005 1 NDC:68084-093-11 1 in 1 BLISTER PACK; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 07/12/2005

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68084-094(NDC:0228-2540) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 250 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) MAGNESIUM STEARATE (UNII: 70097M6I30) MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)

Product Characteristics Color blue (light blue, mottled) Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code R;540 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:68084-094-01 100 in 1 BOX, UNIT-DOSE 08/24/2006 1 NDC:68084-094-11 1 in 1 BLISTER PACK; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074260 08/24/2006

Labeler - American Health Packaging (929561009)

Establishment
Name	Address	ID/FEI	Business Operations
American Health Packaging		929561009	repack(68084-093, 68084-094)

Revised: 2/2019 Document Id: 82bb46c2-9c8f-726c-e053-2a91aa0a0898 34391-3 Set id: 33fbe430-b429-43c0-a3f1-9cf016ff23af Version: 6 Effective Time: 20190225 American Health Packaging

Principal Display Panel-25 Mg/100 Mg ⮝

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:66267-649(NDC:62756-518) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA ANHYDROUS - UNII:KR87B45RGH) CARBIDOPA ANHYDROUS 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2) MAGNESIUM STEARATE (UNII: 70097M6I30) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8)

Product Characteristics Color yellow (yellow to light yellow) Score no score Shape OVAL Size 10mm Flavor Imprint Code 518 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:66267-649-90 90 in 1 BOTTLE; Type 0: Not a Combination Product 12/28/2016

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078536 10/28/2008

Labeler - NuCare Pharmaceuticals, Inc. (010632300)

Establishment
Name	Address	ID/FEI	Business Operations
NuCare Pharmaceuticals, Inc.		010632300	repack(66267-649)

Revised: 12/2016 Document Id: 44bbe727-ed75-5800-e054-00144ff88e88 34391-3 Set id: 44bbe727-ed74-5800-e054-00144ff88e88 Version: 1 Effective Time: 20161228 NuCare Pharmaceuticals, Inc.

No Title 1572448644 ⮝

40-9182
Revised September 2011

Rx Only

Principal Display Panel ⮝

Carbidopa and Levodopa Tablets 25 mg/250 mg 100s Label Text

CARBIDOPA

AND LEVODOPA

Tablets USP

25 mg/250 mg

Each tablet contains:

carbidopa 25 mg*

*(anhydrous equivalent)

levodopa 250 mg

Rx only

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-2866(NDC:0093-0292) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA - UNII:MNX7R8C5VO) CARBIDOPA 10 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code 93;292 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-2866-0 90 in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073618 09/28/1993

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-1334(NDC:0093-0293) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA - UNII:MNX7R8C5VO) CARBIDOPA 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 100 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) D&C YELLOW NO. 10 (UNII: 35SW5USQ3G) FD&C YELLOW NO. 6 (UNII: H77VEI93A8)

Product Characteristics Color YELLOW (mottled-yellow) Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code 93;293;TEVA Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-1334-1 30 in 1 BOTTLE 2 NDC:54868-1334-2 100 in 1 BOTTLE 3 NDC:54868-1334-4 60 in 1 BOTTLE 4 NDC:54868-1334-5 50 in 1 BOTTLE 5 NDC:54868-1334-6 90 in 1 BOTTLE 6 NDC:54868-1334-7 120 in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073589 12/09/1994

CARBIDOPA AND LEVODOPA carbidopa and levodopa tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-2834(NDC:0093-0294) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARBIDOPA (UNII: MNX7R8C5VO) (CARBIDOPA - UNII:MNX7R8C5VO) CARBIDOPA 25 mg LEVODOPA (UNII: 46627O600J) (LEVODOPA - UNII:46627O600J) LEVODOPA 250 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE (UNII: 70097M6I30) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) STARCH, CORN (UNII: O8232NY3SJ) FD&C BLUE NO. 2 (UNII: L06K8R7DQK)

Product Characteristics Color BLUE (mottled-blue) Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code 93;294 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-2834-0 30 in 1 BOTTLE 2 NDC:54868-2834-1 60 in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA073607 12/09/1994

Labeler - Physicians Total Care, Inc. (194123980)

Establishment
Name	Address	ID/FEI	Business Operations
Physicians Total Care, Inc.		194123980	relabel, repack

Revised: 2/2012 Document Id: 55592f54-580b-4049-bbab-d82e7c3255a4 34391-3 Set id: a7b37778-d198-4799-8bf0-92576cff02b9 Version: 2 Effective Time: 20120202 Physicians Total Care, Inc.

Carbidopa And Levodopa Tablets, Usp  ⮝

40-9182

Revised February 2016

Rx Only

Package/label Display Panel ⮝

NDC 60429-153-01