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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
PROCYSBI (NDA-203389)
(CYSTEAMINE BITARTRATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
02/11/2022 (SUPPL-27)
5 Warnings and Precautions
5.4 Fibrosing ColonopathyNewly added subsection:
Fibrosing colonopathy, including colonic stricture formation, has been reported with postmarketing use of PROCYSBI in pediatric and young adult patients with nephropathic cystinosis. Some of these patients had been treated with PROCYSBI for prolonged periods of time. Reported symptoms include: abdominal pain, vomiting, bloody or persistent diarrhea, and fecal incontinence. Evaluate patients with severe, persistent, and/or worsening abdominal symptoms for fibrosing colonopathy. If the diagnosis is
confirmed, permanently discontinue PROCYSBI and switch to immediate-release cysteamine bitartrate capsules. An association between methacrylic acid-ethyl acrylate copolymer (an inactive ingredient in PROCYSBI) and fibrosing colonopathy cannot be ruled out.
6 Adverse Reactions
Addition of the following to the bulleted line listing:
Fibrosing Colonopathy [see Warnings and Precautions (5.4)]
Additions and/or revisions underlined:
The following adverse reactions have been identified during post-approval use of cysteamine bitartrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Musculoskeletal: Joint hyperextension, leg pain, osteopenia, compression fracture, scoliosis, genu valgum [see Warnings and Precautions (5.1)].
Skin: Erythema multiforme bullosa, toxic epidermal necrolysis, Ehlers-Danlos-like syndrome, molluscoid pseudotumors, skin striae, skin fragility [see Warnings and Precautions (5.1, 5.2)].
Gastrointestinal: Fibrosing colonopathy reported with PROCYSBI [see Warnings and Precautions (5.4)].
Central Nervous System: seizures, lethargy, somnolence, depression and encephalopathy [see Warnings and Precautions (5.5)], benign intracranial hypertension (or PTC) and/or papilledema [see Warnings and Precautions (5.7)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditions and/or revisions underlined:
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Fibrosing Colonopathy
Advise patients and caregivers that fibrosing colonopathy has been reported with PROCYSBI. Advise patients to contact their physician immediately if they experience severe, persistent and/or worsening stomach pain, vomiting, bloody or persistent diarrhea, or inability to control bowel movements [see Warnings and Precautions (5.4)].
…
Additions and/or revisions underlined:
What are the possible side effects of PROCYSBI? PROCYSBI can cause serious side effects, including:
Skin, bone, and joint problems. People treated with high doses of cysteamine bitartrate may develop abnormal changes of their skin and bones. These changes may include stretch marks, bone injuries (such as fractures), bone deformities, and joint problems. Check your skin while taking PROCYSBI. Tell your doctor if you notice any skin changes or problems with your bones or joints. Your doctor will check you for these problems.
Skin rash. Skin rash is common with cysteamine bitartrate and may sometimes be severe. Tell your doctor right away if you get a skin rash. Your dose of PROCYSBI may need to be decreased until the rash goes away. If the rash is severe, your doctor may tell you to stop taking PROCYSBI.
- Stomach and bowel (intestinal) problems. Some people who take other medicines that contain cysteamine bitartrate may develop ulcers and bleeding in their stomach or bowel. People treated with PROCYSBI may also develop abnormal swelling and narrowing of the large bowel which must be treated right away. Tell your doctor right away if you get abdominal pain, nausea, vomiting, loss of appetite, weight loss, bloody or persistent diarrhea, or are vomiting blood or have bowel moments that you cannot control.
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06/24/2020 (SUPPL-23)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(Additions and/or revisions underlined)
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Administration
Advise patients and caregivers to follow the instruction below for taking PROCYSBI.
Capsules:
Swallow PROCYSBI capsules whole. Do not crush or chew capsules or capsule contents.
Take PROCYSBI capsules with fruit juice (except grapefruit juice) or water.
For patients who cannot swallow the capsules, the capsules can be opened and the capsule contents sprinkled on and mixed in applesauce, berry jelly or fruit juice (except grapefruit juice) and administered orally.
- For patients with a gastrostomy tube, follow the instructions in the Instructions for Use
Do not crush or chew the granules.
Sprinkle and mix intact granules from on applesauce, berry jelly or fruit juice (except grapefruit juice) and administer orally.
For patients with a gastrostomy tube, follow the instruction in the Instructions for Use
Oral
Granules:
Administer PROCYSBI at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate.
Do not eat for at least 2 hours before and for at least 30 minutes after taking PROCYSBI. If unable to take PROCYSBI without eating, take with food but limit the amount of food to approximately 4 ounces (1?2 cup) 1 hour before through 1 hour after administration. Avoid high fat food close to dosing of PROCYSBI.
Avoid drinking alcohol while taking PROCYSBI.
Take PROCYSBI consistently and to not miss doses. If a dose is missed, take the dose as soon as possible up to 8 hours after the scheduled time. However, if a dose is missed and the next scheduled dose is due in less than 4 hours, do not take the missed dose, and to take the next dose at the usual scheduled time. Do not take 2 doses at one time to make up for a missed dose [see Dosage and Administration (2.6)].
Storage
Advise patients and caregivers to keep PROCYSBI in a dry place. Protect from moisture. For bottles, keep PROCYSBI delayed-release capsules in the original bottle. Do not remove the desiccant or oxygen absorber from the bottle. Do not store PROCYSBI delayed-release oral granules in opened packets [see How Supplied/Storage and Handling (16)].
(Additions and/or revisions underlined)
…
Before taking PROCYSBI, tell your doctor about all of your medical conditions, including if you:
drink alcohol.
have a skin rash or bone problems.
have or have had stomach or bowel (intestinal) problems including ulcers or bleeding.
have a history of seizures, lack of energy, unusual sleepiness, depression, or changes in your ability to think clearly.
have liver or blood problems.
are pregnant or plan to become pregnant. It is not known if PROCYSBI will harm your unborn baby. Tell your doctor right away if you think that you are pregnant. Talk with your doctor about the benefits and risks of taking PROCYSBI during pregnancy.
- are breastfeeding or plan to breastfeed. You should not breastfeed during treatment with PROCYSBI. Talk with your doctor about the best way to feed your baby if you take PROCYSBI.
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
How should I take PROCYSBI?
Read the “Instructions for Use” that comes with PROCYSBI for information about the right way to prepare and take PROCYSBI.
Take PROCYSBI exactly as your doctor tells you to.
Your doctor may start you on a low dose of PROCYSBI and slowly increase your dose to help avoid side effects, especially if you have not taken a medicine that contains cysteamine bitartrate before.
Do not change your dose of PROCYSBI unless your doctor tells you to.
PROCYSBI is taken 2 times each day, every 12 hours.
Take PROCYSBI the same way each time, either without eating or with a small amount of food, as follows:
If you take PROCYSBI without eating, do not eat for at least 2 hours before taking PROCYSBI and at least 30 minutes after taking PROCYSBI.
If you are not able to take PROCYSBI without eating, you can eat a small amount of food (½ cup) within 1 hour before you take PROCYSBI through 1 hour after you take it.
Avoid eating foods that are high in fat close to the time that you will take a dose of PROCYSBI.
Talk to your doctor or pharmacist if you have questions about how to take PROCYSBI.
PROCYSBI is available as capsules in a bottle and oral granules in packets.
Capsules:
Swallow PROCYSBI capsules whole. Do not crush or chew capsules or capsule contents.
Take the PROCYSBI capsule whole with fruit juice (except for grapefruit juice) or water.
If PROSCYBI capsules cannot be swallowed whole, the capsule may be opened and the contents sprinkled on and mixed in applesauce, berry jelly or fruit juice (except grapefruit juice) and taken by mouth.
- Read the “Instructions for Use” if you have a gastrostomy tube (G-tube).
Granules:
Sprinkle and mix PROCYSBI oral granules on applesauce, berry jelly or fruit juice (except grapefruit juice) and take by mouth. Do not crush or chew oral granules.
Read the “Instructions for Use” if you have a gastrostomy tube (G-tube).
Take PROCYSBI at least 1 hour before or 1 hour after you take medicines that contain bicarbonate or carbonate.
If you miss a dose, take it as soon as possible, up to 8 hours after the scheduled time of the missed dose. If it is less than 4 hours of the time the next dose is due, skip the missed dose. Take the next dose at your regularly scheduled time. Do not take 2 doses at one time to make up for a missed dose.
If you take too much PROCYSBI, call your doctor or go to the nearest hospital emergency room right away.
- Your doctor should do blood tests to measure the amount of cystine inside your white blood cells or to measure the amount of PROCYSBI in your blood before you start taking it and regularly during treatment with PROCYSBI. This will help your doctor to prescribe the dose of PROCYSBI that is right for you.
Take supplements if prescribed by your doctor, such as salt or mineral replacement supplements, vitamin D, or thyroid hormone.
…
The most common side effects with PROCYSBI include:
vomiting nausea stomach (abdominal) pain
pink eye diarrhea cold
tiredness flu headache
problems with body salts or electrolytes infection of ear, nose or throat
- joint pain
These are not all the possible side effects of PROCYSBI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of PROCYSBI.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PROCYSBI for a condition for which it was not prescribed. Do not give PROCYSBI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about PROCYSBI that is written for health professionals.
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05/31/2019 (SUPPL-22)
6 Adverse Reactions
6.1 Clinical Trials Experience(additions and revisions underlined)
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Clinical Trials Experience with PROCYSBI in Patients Switched from Immediate-Release Cysteamine Bitartrate
Sixty-two patients with nephropathic cystinosis (38 males and 24 females) received PROCYSBI in two clinical trials at doses ranging from 0.29 grams/m2 per day to 2.19 grams/m2 per day. All patients were switched from immediate-release cysteamine to PROCYSBI. Forty-three patients, ages 6 to 26 years old, received PROCYSBI in an 8-week, open-label, randomized, cross-over trial comparing PROCYSBI to immediate-release cysteamine bitartrate. Forty of 43 patients continued PROCYSBI treatment in an open-label extension trial (36 patients were treated with PROCYSBI for longer than 2 years, and 20 patients were treated for longer than 5 years). An additional 19 patients (6 renal transplanted patients and 13 patients aged 2 to 6 years) were enrolled directly into this trial (12 patients were treated with PROCYSBI forlonger than 2 years, and 9 patients were treated for longer than 5 years).
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In the open-label extension trial (N=59), the most commonly reported adverse reactions (>15%) were vomitin g, headache, diarrhea, nausea, conjunctivitis, influenza, gastroenteritis, nasopharyngitis, abdominal pain, dehydration, ear infection, upper respiratory tract infection, fatigue, arthralgia, cough, and pain in extremity.
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12/22/2017 (SUPPL-20)
6 Adverse Reactions
6.1 Clinical Trials Experience(Additions and/or revisions are underlined)
The data described below reflect exposure to cysteamine in 345 patients with nephropathic cystinosis (246 patients receiving immediate-release cysteamine as cysteamine hydrochloride or phosphocysteamine, and 80 patients receiving PROCYSBI) in open-label clinical trials.
Clinical Trials Experience with PROCYSBI in Patients Switched from Immediate-Release Cysteamine Bitartrate
Sixty-two patients with nephropathic cystinosis (38 males and 24 females) received PROCYSBI in two clinical trials at doses ranging from 0.29 grams/m2 per day to 2.19 grams/m2 per day. All patients were switched from immediate-release cysteamine to PROCYSBI. Forty-three patients, ages 6 to 26 years old, received PROCYSBI in an 8-week, open-label, randomized, cross-over trial comparing PROCYSBI to immediate-release cysteamine bitartrate. Forty of 43 patients continued PROCYSBI treatment in an open-label extension trial, and were treated with PROCYSBI for longer than 2 years. An additional 19 patients (6 renal transplanted patients and 13 patients aged 2 to 6 years) were enrolled directly into this trial and were treated with PROCYSBI for up to 18 months.
In the open-label, randomized, cross-over trial, a higher incidence of adverse reactions was reported in patients during the PROCYSBI treatment period compared with the immediate-release cysteamine bitartrate treatment period (see Table 2)…
Table 2: Adverse Reactions in greater than or equal to 5% of Patients with Nephropathic Cystinosis in a Randomized, Cross-Over Trial
In the open-label, randomized, cross-over trial, a higher incidence of adverse reactions was reported in patients during the PROCYSBI treatment period compared with the immediate-release cysteamine bitartrate treatment period (see Table 2)…
Clinical Trials Experience with PROCYSBI in Cysteamine-Naïve Patients
Seventeen cysteamine-naïve patients (fifteen patients between the ages of 1 and 5 years, one 9-year old and one 22-year old) received PROCYSBI in an open-label clinical trial. Serious adverse reactions occurring in at least 2 patients (greater than 10%) were: gastroenteritis/viral gastroenteritis (n=6), vomiting (n=4), and electrolyte imbalance (n=2). Three patients with serious adverse reactions of gastroenteritis also had dehydration. Common adverse reactions reported at a frequency of greater than10% (occurring in at least 2 patients) are shown in Table 3.
Table 3: Adverse Reactions in >10% of Patients with Nephropathic Cystinosis Naïve to Cysteamine Treatment in an Open-Label Trial
7 Drug Interactions
7.1 Drugs that Increase Gastric pH(Additions and/or revisions are underlined)
Drugs that increase the gastric pH (e.g., medications containing bicarbonate or carbonate) may alter the pharmacokinetics of cysteamine due to the premature release of cysteamine from PROCYSBI and increase WBC cystine concentration. Concomitant administration of 20 mg omeprazole did not affect the pharmacokinetics of cysteamine when PROCYSBI was administered with 240 mL of orange juice or with 240 mL of water…
8 Use in Specific Populations
8.4 Pediatric Use(Additions and/or revisions are underlined)
The safety and effectiveness of PROCYSBI have been established in pediatric patients 1 year of age and older for the treatment of nephropathic cystinosis. Use of PROCYSBI is supported by evidence from patients switched to PROCYSBI from immediate-release cysteamine bitartrate in two trials: an open-label, randomized, cross-over trial in adults and pediatric patients aged 6 years and older (n=43) and an open- label extension trial in pediatric patients aged 2 years and older (n=59). Another open-label trial was conducted in cysteamine naïve pediatric patients 1 year to less than 6 years of age (n=15). The safety profile in pediatric patients was similar to adults. In patients less than 6 years of age, vomiting occurred in 12/15 cysteamine treatment naïve patients compared to 8/13 patients switched from immediate-release cysteamine to PROCYSBI.
The safety and effectiveness of PROCYSBI have not been established in patients less than 1 year of age.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
Administration
Advise patients and caregivers to follow the instruction below for taking
Take PROCYSBI capsules with fruit juice (except grapefruit juice) or water
09/24/2017 (SUPPL-17)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(additions underlined)
…
Administration
· Advise patients and caregivers to follow the instruction below for taking PROCYSBI capsules whole.
o Swallow PROCYSBI capsules whole. Do not crush or chew capsules or capsule contents
o Take PROCYSBI capsules with fruit juice (except grapefruit juice)
· Administer PROCYSBI at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate
· Do not eat for at least 2 hours before and for at least 30 minutes after taking PROCYSBI. If unable to take PROCYSBI without eating, take with food but limit the amount of food to approximately 4 ounces (1?2 cup) 1 hour before through 1 hour after administration. Avoid high fat food close to dosing of PROCYSBI
· Avoid drinking alcohol while taking PROCYSBI
· For patients who have difficulty swallowing capsules or those with a Gastrostomy (G) tube, follow the instructions in the Instructions for Use for opening the capsule and administering with food or liquid.
Take PROCYSBI consistently and to not miss doses. If a dose is missed, take the dose as soon as possible up to 8 hours after the scheduled time. However, if a dose is missed and the next scheduled dose is due in less than 4 hours, do not take the missed dose, and to take the next dose at the usual scheduled time. Do not take 2 doses at one time to make up for a missed dose.
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