JAMP LEVOCARB

1 Dosing Considerations In order to reduce the incidence of adverse reactions and achieve maximal benefit, therapy with JAMP Levocarb (levodopa and carbidopa tablets) must be individualized JAMP Levocarb (Levodopa and Carbidopa Tablets) Page 6 of 40 and drug administration must be continuously matched to the needs and tolerance of the patient.

It should be borne in mind that the therapeutic range of JAMP Levocarb is narrower than that of levodopa alone because of its greater milligram potency. Therefore, titration and adjustment of dosage should be made in small steps and the dosage ranges recommended should usually not be exceeded.

The appearance of involuntary movements should be regarded as a sign of levodopa toxicity and as an indication of overdosage, requiring dose reduction. Treatment should, therefore, aim at maximal benefit without dyskinesias. • If a patient being treated with levodopa is switched to therapy with JAMP Levocarb, levodopa must be discontinued at least twelve hours or more before therapy with JAMP Levocarb is initiated.

• Although the administration of carbidopa permits control of Parkinson’s disease with much lower doses of levodopa, there is no conclusive evidence at present that this is beneficial other than reducing nausea and vomiting, permitting more rapid titration, and providing a somewhat smoother response to levodopa.

Carbidopa does not decrease adverse reactions due to central effects of levodopa. , dyskinesias, may occur at lower dosages and sooner during therapy with JAMP Levocarb than with levodopa. • JAMP Levocarb tablets are available in a 4:1 ratio (JAMP Levocarb 100 mg / 25 mg) and in a 10:1 ratio of levodopa to carbidopa (JAMP Levocarb 100 mg / 10 mg and 250 mg / 25 mg).

Tablets of the two ratios may be given separately or combined as needed to provide the optimal dosage. • Dividing the tablets along the score line may not give exact equal half doses. • Studies have shown that peripheral dopa decarboxylase is saturated by carbidopa at doses between 70 to 150 mg per day.

Patients receiving less than 70 mg per day of carbidopa are more likely to experience nausea and vomiting. Experience with total daily dosages of carbidopa greater than 200 mg is limited. , less than 700 mg, JAMP Levocarb 100 mg / 25 mg may be helpful.

2 Recommended Dose and Dosage Adjustment • Induction of Therapy in Patients Not Receiving Levodopa Dosage is best initiated with one tablet of JAMP Levocarb 100 mg / 25 mg three times a day. This dosage schedule provides 75 mg of carbidopa per day.

). Literature and postmarketing reports have described a very rare addictive pattern of dopamine replacement therapy, in which patients use doses in excess of those required to control their motor symptoms. Review of treatment is recommended if such symptoms develop.

Hallucinations:

Hallucinations and confusion are known side effects of treatment with dopaminergic agents, including levodopa. Patients should be aware of the fact that hallucinations (mostly visual) can occur.

Skin 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 JAMP Levocarb (Levodopa and Carbidopa Tablets) Page 12 of 40 factors, such as drugs used to treat Parkinson’s disease, is unclear.

For the reasons stated above, patients and healthcare providers are advised to monitor for melanomas frequently and on a regular basis when using JAMP Levocarb for any indication. , dermatologists). 1 Pregnant Women Although the effects of JAMP Levocarb on human pregnancy and lactation are unknown, both levodopa and combinations of carbidopa and levodopa have caused visceral and skeletal malformations in rabbits (see 16 NON-CLINICALTOXICOLOGY, Teratologic and Reproductive Studies).

Therefore, use of JAMP Levocarb in women of child-bearing potential requires that the anticipated benefits of the drug be weighed against possible hazards to the mother and to the fetus. 2 Breast-feeding It is not known whether carbidopa is excreted in human milk.

In a study of one nursing mother with Parkinson’s disease, excretion of levodopa in breast milk was reported. JAMP Levocarb should not be given to nursing mothers unless the anticipated benefits to the mother outweigh the potential hazards to the infant.

General When patients already receiving levodopa are switched to JAMP Levocarb, levodopa must be discontinued for at least 12 hours or more before JAMP Levocarb is started. JAMP Levocarb should be substituted at a dosage that will provide approximately 20% of the previous levodopa dosage (see 4 DOSAGE AND ADMINISTRATION).

Patients who are taking JAMP Levocarb should be instructed not to take additional levodopa unless it is prescribed by the physician. Periodic evaluations of hepatic, hematopoietic, cardiovascular and renal function are JAMP Levocarb (Levodopa and Carbidopa Tablets) Page 10 of 40 recommended during extended therapy with JAMP Levocarb (levodopa and carbidopa tablets).

Physical Activity:

Patients who improve while on therapy with JAMP Levocarb should increase physical activities gradually, with caution, consistent with other medical considerations such as the presence of osteoporosis or phlebothrombosis. Cardiovascular Care should be exercised in administering JAMP Levocarb to patients with a history of myocardial infarction or who have 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. Gastrointestinal JAMP Levocarb should be administered cautiously to patients with a history of peptic ulcer disease due to the possibility of upper gastrointestinal hemorrhage.

Neurologic The levodopa induced involuntary movements and 'on and off' phenomenon may appear earlier with combination therapy. As with levodopa, JAMP Levocarb may cause involuntary movements and mental disturbances. These reactions are thought to be due to increased brain dopamine following administration of levodopa.

Because carbidopa permits more levodopa to reach the brain and thus, more dopamine to be formed, dyskinesias may occur at lower dosages and sooner with JAMP Levocarb than with levodopa. The occurrence of dyskinesias may require dosage reduction.

• JAMP Levocarb is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING of the product monograph.

• Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with JAMP Levocarb. These inhibitors must be discontinued at least two weeks prior to initiating therapy with JAMP Levocarb. g. selegiline HCl) (see 9 DRUG INTERACTIONS, Drug-Drug Interactions, Psychoactive Drugs) at the manufacturer’s recommended dose which maintains selectivity for MAO type B.

• JAMP Levocarb should not be administered to patients with clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematologic, hepatic, pulmonary (including bronchial asthma), or renal disease; or to patients with narrow angle glaucoma.

, epinephrine, norepinephrine or isoproterenol). • Because levodopa may activate a malignant melanoma, JAMP Levocarb should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma. JAMP Levocarb (Levodopa and Carbidopa Tablets) Page 5 of 40