Rytary

Rytary contains a combination of carbidopa and levodopa.

Rytary extended-release capsules are used to treat symptoms of Parkinson's disease, such as muscle stiffness, tremors, spasms, and poor muscle control. Parkinson's disease may be caused by low levels of a chemical called dopamine in the brain.

Rytary is also used to treat parkinsonism that follows carbon monoxide poisoning or manganese intoxication, and post-encephalitic parkinsonism.

Rytary is not interchangeable with other carbidopa and levodopa products. Doses cannot be swapped on a 1:1 basis, so do not switch between Rytary and another carbidopa and levodopa medicine unless your doctor tells you to.

Take Rytary exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

• Take your doses at regular intervals to keep a steady amount of the medicine in your body. Rytary is usually taken 3 times a day, and up to 5 times a day if needed.
• Swallow the capsule whole. Do not chew, divide, or crush it. If you find capsules hard to swallow, you can carefully twist apart both halves, sprinkle all of the contents onto 1 to 2 tablespoons of applesauce, and take it straight away. Do not save the mixture for later.
• Rytary can be taken with or without food. A high-fat, high-calorie meal can delay the medicine from working by 2 to 3 hours, so you may want to take your first dose of the day 1 to 2 hours before eating.
• Do not take other carbidopa and levodopa preparations alongside Rytary unless your doctor tells you to. Taking Rytary with other levodopa medicines has not been studied.

It may take up to several weeks before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after a few weeks of treatment. Also tell your doctor if the effects of this medication seem to wear off quickly between doses.

If you use Rytary long-term, you may need frequent medical tests. Your doctor may check your liver, blood counts, heart and kidney function during extended treatment.

This medicine can affect the results of certain laboratory tests. It can give a false-positive result for ketones in urine and a false-negative result on some urine glucose tests, and it can affect tests for catecholamines. Tell any doctor who treats you that you are using Rytary.

Do not stop using Rytary suddenly. Ask your doctor how to safely stop this medicine.

Store at room temperature away from moisture, heat, and light.

Do not use Rytary if you are taking a nonselective MAO inhibitor, such as phenelzine or tranylcypromine, or if you have taken one in the past 2 weeks. Taking these medicines together can cause dangerously high blood pressure.

Rytary may reduce vitamin B6 levels in your body. Higher dosages are more likely to increase the risk of vitamin B6 deficiency, which may cause seizures. These seizures are typically resistant to traditional anti-seizure medications but usually resolve with vitamin B6 administration. Other symptoms of vitamin B6 deficiency may include depression, confusion, cheilosis (cracking, crusting, or scaling in the corners of the mouth), glossitis (inflammation of the tongue), dermatitis, anemia, or neuropathy (nerve pain). Let your healthcare provider know if you develop any of these symptoms. Your healthcare provider should evaluate your vitamin B6 levels before starting Rytary and regularly while you are taking it, or if symptoms of vitamin B6 deficiency develop. You may need to take vitamin B6 supplements, and you can keep taking Rytary while you do.

Some people taking Rytary have fallen asleep suddenly during normal daytime activities, including while driving, sometimes with no warning that they were sleepy. This has been reported more than a year after starting treatment. Tell your doctor about any daytime sleepiness before you start Rytary and while you take it, and do not drive until you know how this medicine affects you.

Do not stop taking Rytary suddenly. Stopping abruptly or cutting your dose quickly can cause a serious reaction with fever, severe muscle stiffness, confusion, and unstable blood pressure or heart rate. Your doctor will taper your dose if you need to stop.

Heart problems caused by reduced blood flow have occurred in people taking Rytary, mostly in those who already had ischemic heart disease or risk factors for it. In a study in early Parkinson's disease, these events affected 2.4% of people taking Rytary compared with 1.1% taking placebo.

Rytary can cause hallucinations and psychosis, which usually start soon after treatment begins and may improve if the dose is reduced. Because of the risk of making psychosis worse, Rytary should not be used by people with a major psychotic disorder. Medicines used to treat psychosis can also make Parkinson's symptoms worse and make Rytary less effective.

Do not take Rytary if you:

• are allergic to carbidopa or levodopa
• have taken a nonselective MAO inhibitor in the past 2 weeks. A dangerous drug interaction could occur. These medicines must be stopped at least 2 weeks before starting Rytary
• have narrow-angle glaucoma.

To make sure Rytary is safe for you, tell your doctor about all your medical conditions, including if you have:

• heart disease, high blood pressure, or a previous heart attack, especially if you have an irregular heartbeat, as your heart may need monitoring when your dose is first adjusted;
• liver or kidney disease;
• an endocrine (hormonal) disorder;
• asthma, chronic obstructive pulmonary disease (COPD), or another breathing disorder;
• a stomach or intestinal ulcer. Rytary may increase the chance of bleeding in the upper digestive tract if you have a history of peptic ulcer;
• wide-angle glaucoma. This medicine can raise the pressure inside your eye, so your eye pressure should be checked after you start it;
• depression, mental illness, or psychosis;
• a sleep disorder, or if you take medicines that make you drowsy; or
• a known vitamin B6 deficiency.

People with Parkinson's disease have a 2-fold to roughly 6-fold higher risk of developing skin cancer (melanoma) than the general population. It is not clear whether this is due to the disease itself or to the medicines used to treat it. Watch your skin for new or changing moles and have regular skin examinations, ideally by a dermatologist.

Your doctor will check your vitamin B6 levels before you start Rytary.

Tell your doctor if you are pregnant or planning to become pregnant. There are no adequate data on the risk to a pregnancy from Rytary, but in animal studies, carbidopa and levodopa caused birth defects at doses similar to those used in people.

Tell your doctor if you are breastfeeding. Levodopa passes into breast milk, and it can also reduce milk production because it lowers prolactin levels. The effects on a breastfed baby are not known.

Rytary is not approved for use in children.

Get emergency medical help if you have signs of an allergic reaction to Rytary: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);
• new or worsening uncontrolled movements (dyskinesia), or worsening tremors;
• severe or ongoing vomiting or diarrhea;
• confusion, hallucinations, paranoia, agitation, or unusual changes in mood or behavior;
• depression or suicidal thoughts;
• severe nervous system reaction — very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;
• chest pain or other signs of a heart problem;
• cracking, crusting, or scaling in the corners of your mouth;
• inflammation of your tongue;
• skin rash, or a new or changing mole;
• anemia; or
• neuropathy (nerve pain).

You may have increased sexual urges, unusual urges to gamble, urges to spend money, binge eating, or other intense urges while taking this medicine, and find them hard to control. You may not recognise these changes yourself, so ask family or carers to tell you if they notice them, and talk with your doctor if this occurs. Reducing the dose or stopping the medicine has stopped these urges in some people.

You may notice that your sweat, urine, or saliva appears dark in color, such as red, brown, or black. This is not a harmful side effect, but it may cause staining of your clothes or bed sheets.

Common side effects

Common Rytary side effects, with how often they occurred in a study in early Parkinson's disease, may include:

• nausea (up to 20%), vomiting (up to 5%), constipation (up to 6%);
• dizziness (up to 19%), headache (up to 17%);
• sleep problems (up to 9%), strange dreams (up to 6%);
• dry mouth (up to 7%);
• jerky or twisting muscle movements (dyskinesia, up to 5%);
• anxiety (up to 5%); or
• low blood pressure on standing (up to 5%), which can cause light-headedness, nausea, sweating or fainting — get up slowly after sitting or lying down.

In studies, 12% of people taking Rytary for early Parkinson's disease stopped treatment because of side effects, most often nausea, dizziness, and vomiting.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual adult dose for Parkinson's disease

The optimum dose is found by careful individual titration. All doses are expressed as carbidopa-levodopa.

Before starting, your vitamin B6 level should be checked, and topped up if it is low. Treatment can begin and continue while you take vitamin B6 supplements.

People who have not taken levodopa before:

• Starting dose: 23.75 mg/95 mg orally 3 times a day for 3 days.
• On the fourth day, the dose may be increased to 36.25 mg/145 mg 3 times a day.
• Depending on response and tolerability, the dose may be increased to a maximum of 97.5 mg/390 mg 3 times a day.
• The dosing frequency may be increased from 3 times a day up to a maximum of 5 times a day if needed and tolerated.
• Maximum daily dose: 612.5 mg/2,450 mg.

Switching from immediate-release carbidopa-levodopa to Rytary:

• First work out the current total daily dose of levodopa, then use the table below. Starting doses are divided and given 3 times a day.

After switching, any combination of the four capsule strengths can be used to reach the best dose. Other Parkinson's disease medicines should stay the same while the Rytary dose is being adjusted.

Comments

• Peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 mg to 100 mg per day. Patients receiving less than this are more likely to experience nausea and vomiting. Experience with carbidopa doses above 200 mg per day is limited.
• Rytary is not interchangeable with other carbidopa-levodopa products.
• For patients taking a catechol-O-methyl transferase (COMT) inhibitor such as entacapone, the initial total daily dose of levodopa in Rytary may need to be increased.
• When stopping, the daily dose should be tapered rather than stopped abruptly.

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Get your prescription refilled before you run out of medicine completely.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms come from too much dopamine activity and may include confusion or other nervous system effects, uncontrolled movements, hallucinations or psychosis, low blood pressure and a fast heartbeat. Heart rhythm monitoring may be needed.

Avoid driving or hazardous activities until you know how this medicine will affect you. Your reactions could be impaired, and this medicine can make you suddenly fall asleep. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Avoid drinking alcohol, as it can increase drowsiness and is not recommended with certain forms of this medicine.

Iron supplements and multivitamins containing iron can bind to carbidopa and levodopa in the gut and reduce how much medicine your body absorbs. A meal high in protein, or one high in fat and calories, can also delay or reduce absorption. You do not need to avoid these foods altogether, but tell your doctor if your medicine seems less effective, and talk with your doctor or a dietitian about how to space meals and supplements around your doses.

Tell your doctor about all your current medicines and any medicine you start or stop using. In particular:

• Nonselective MAO inhibitors such as phenelzine and tranylcypromine must not be taken with Rytary, and must be stopped at least 2 weeks before starting it, because blood pressure can rise dangerously.
• Selective MAO-B inhibitors such as rasagiline and selegiline can be used with Rytary but may cause low blood pressure on standing, so you will be monitored.
• Medicines that block dopamine — including phenothiazines, butyrophenones, risperidone and metoclopramide — and isoniazid can make Rytary less effective and your Parkinson's symptoms worse.
• Iron salts and multivitamins containing iron reduce how much carbidopa and levodopa your body absorbs, which can make your symptoms worse.
• COMT inhibitors such as entacapone affect the levodopa dose you need when starting Rytary.

Other drugs may interact with carbidopa and levodopa, including prescription and over-the-counter medicines, vitamins, and herbal products.

Active ingredients: levodopa 95 mg; carbidopa 23.75 mg (as carbidopa hydrate, expressed as anhydrous carbidopa)

Inactive ingredients: microcrystalline cellulose, mannitol, tartaric acid, ethylcellulose, hypromellose 2910 (6 mPa·s), sodium starch glycolate type A (potato), sodium lauryl sulfate, povidone, talc, methacrylic acid–methyl methacrylate copolymer (1:1), methacrylic acid–methyl methacrylate copolymer (1:2), triethyl citrate, croscarmellose sodium, magnesium stearate, gelatin, titanium dioxide, FD&C blue no. 2, ferric oxide yellow, butyl alcohol, alcohol, isopropyl alcohol, propylene glycol, shellac, ammonia.

Rytary (carbidopa and levodopa) is manufactured by Amneal Pharmaceuticals LLC.