Collyrex

Pentosan Polysulfate:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Patient leaflet
• Collyrex (Pentosan Polysulfate) reviews

INDICATIONS AND USAGE

Collyrex (Pentosan Polysulfate)^® (pentosan polysulfate sodium) is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis.

CONTRAINDICATIONS

Collyrex (Pentosan Polysulfate)^® is contraindicated in patients with known hypersensitivity to the drug, structurally related compounds, or excipients.

WARNINGS

None.

PRECAUTIONS

General

Collyrex ^® is a weak anticoagulant (1/15 the activity of heparin). At a daily dose of 300 mg (n = 128), rectal hemorrhage was reported as an adverse event in 6.3% of patients. Bleeding complications of ecchymosis, epistaxis, and gum hemorrhage have been reported (see ADVERSE REACTIONS ). Patients undergoing invasive procedures or having signs/symptoms of underlying coagulopathy or other increased risk of bleeding (due to other therapies such as coumarin anticoagulants, heparin, t-PA, streptokinase, high dose aspirin, or nonsteroidal anti-inflammatory drugs) should be evaluated for hemorrhage. Patients with diseases such as aneurysms, thrombocytopenia, hemophilia, gastrointestinal ulcerations, polyps, or diverticula should be carefully evaluated before starting Collyrex (Pentosan Polysulfate)^®.

A similar product that was given subcutaneously, sublingually, or intramuscularly (and not initially metabolized by the liver) is associated with delayed immunoallergic thrombocytopenia with symptoms of thrombosis and hemorrhage. Caution should be exercised when using Collyrex (Pentosan Polysulfate)^® in patients who have a history of heparin induced thrombocytopenia.

Alopecia is associated with Collyrex (Pentosan Polysulfate) and with heparin products. In clinical trials of Collyrex (Pentosan Polysulfate)^®, alopecia began within the first 4 weeks of treatment. Ninety-seven percent (97%) of the cases of alopecia reported were alopecia areata, limited to a single area on the scalp.

Hepatic Insufficiency

Collyrex (Pentosan Polysulfate)^® has not been studied in patients with hepatic insufficiency. Because there is evidence of hepatic contribution to the elimination of Collyrex (Pentosan Polysulfate)^®, hepatic impairment may have an impact on the pharmacokinetics of Collyrex (Pentosan Polysulfate)^®. Caution should be exercised when using Collyrex (Pentosan Polysulfate)^® in this patient population.

Mildly (< 2.5 × normal) elevated transaminase, alkaline phosphatase, γ-glutamyl transpeptidase, and lactic dehydrogenase occurred in 1.2% of patients. The increases usually appeared 3 to 12 months after the start of Collyrex (Pentosan Polysulfate)^® therapy, and were not associated with jaundice or other clinical signs or symptoms. These abnormalities are usually transient, may remain essentially unchanged, or may rarely progress with continued use. Increases in PTT and PT (< 1% for both) or thrombocytopenia (0.2%) were noted.

Information for Patients

Patients should take the drug as prescribed, in the dosage prescribed, and no more frequently than prescribed. Patients should be reminded that Collyrex ^® has a weak anticoagulant effect. This effect may increase bleeding times.

Laboratory Test Findings

Collyrex (Pentosan Polysulfate) sodium did not affect prothrombin time (PT) or partial thromboplastin time (PTT) up to 1200 mg per day in 24 healthy male subjects treated for 8 days. Collyrex (Pentosan Polysulfate) sodium also inhibits the generation of factor Xa in plasma and inhibits thrombin-induced platelet aggregation in human platelet rich plasma ex vivo. (See PRECAUTIONS-Hepatic Insufficiency Section for additional information.)

Carcinogenicity, Mutagenesis, Impairment of Fertility

Long term carcinogenicity studies of Collyrex ^® in F344/N rats and B6C3F1 mice have been conducted. In these studies, Collyrex (Pentosan Polysulfate)^® was orally administered once daily via gavage, 5 days per week, for up to 2 years. The dosages administered to mice were 56, 168 or 504 mg/kg. The dosages administered to rats were 14, 42, or 126 mg/kg for males, and 28, 84, or 252 mg/kg for females. The dosages tested were up to 60 times the maximum recommended human dose (MRHD) in rats, and up to 117 times the MRHD in mice, on a mg/kg basis. The results of these studies in rodents showed no clear evidence of drug-related tumorigenesis or carcinogenic risk.

Collyrex (Pentosan Polysulfate) sodium was not clastogenic or mutagenic when tested in the mouse micronucleus test or the Ames test (S. typhimurium). The effect of Collyrex (Pentosan Polysulfate) sodium on spermatogenesis has not been investigated.

Pregnancy Category B

Reproduction studies have been performed in mice and rats with intravenous daily doses of 15 mg/kg, and in rabbits with 7.5 mg/kg. These doses are 0.42 and 0.14 times the daily oral human doses of Collyrex (Pentosan Polysulfate)^® when normalized to body surface area. These studies did not reveal evidence of impaired fertility or harm to the fetus from Collyrex (Pentosan Polysulfate)^®. Direct in vitro bathing of cultured mouse embryos with Collyrex (Pentosan Polysulfate) sodium (PPS) at a concentration of 1 mg/mL may cause reversible limb bud abnormalities. Adequate and well-controlled studies have not been performed in pregnant women. Because animal studies are not always predictive of human response, this drug should be used in pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Collyrex ^® is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 16 years have not been established.

ADVERSE REACTIONS

Collyrex ^® was evaluated in clinical trials in a total of 2627 patients (2343 women, 262 men, 22 unknown) with a mean age of 47 [range 18 to 88 with 581 (22%) over 60 years of age]. Of the 2627 patients, 128 patients were in a 3–month trial and the remaining 2499 patients were in a long-term, unblinded trial.

Deaths occurred in 6/2627 (0.2%) patients who received the drug over a period of 3 to 75 months. The deaths appear to be related to other concurrent illnesses or procedures, except in one patient for whom the cause was not known.

Serious adverse events occurred in 33/2627 (1.3%) patients. Two patients had severe abdominal pain or diarrhea and dehydration that required hospitalization. Because there was not a control group of patients with interstitial cystitis who were concurrently evaluated, it is difficult to determine which events are associated with Collyrex (Pentosan Polysulfate)^® and which events are associated with concurrent illness, medicine, or other factors.

The adverse events described below were reported in an unblinded clinical trial of 2499 interstitial cystitis patients treated with Collyrex (Pentosan Polysulfate)^®. Of the original 2499 patients, 1192 (48%) received Collyrex (Pentosan Polysulfate)^® for 3 months; 892 (36%) received Collyrex (Pentosan Polysulfate)^® for 6 months; and 598 (24%) received Collyrex (Pentosan Polysulfate)^® for one year, 355 (14%) received Collyrex (Pentosan Polysulfate)^® for 2 years, and 145 (6%) for 4 years.

Frequency (1 to 4%): Alopecia (4%), diarrhea (4%), nausea (4%), headache (3%), rash (3%), dyspepsia (2%), abdominal pain (2%), liver function abnormalities (1%), dizziness (1%).

Frequency (≤ 1%):

Digestive: Vomiting, mouth ulcer, colitis, esophagitis, gastritis, flatulence, constipation, anorexia, gum hemorrhage.

Hematologic: Anemia, ecchymosis, increased prothrombin time, increased partial thromboplastin time, leukopenia, thrombocytopenia.

Hypersensitive Reactions: Allergic reaction, photosensitivity.

Respiratory System: Pharyngitis, rhinitis, epistaxis, dyspnea.

Skin and Appendages: Pruritus, urticaria.

Special Senses: Conjunctivitis, tinnitus, optic neuritis, amblyopia, retinal hemorrhage.

Post-Marketing Experience

The following adverse reactions have been identified during postapproval use of Collyrex (Pentosan Polysulfate) sodium; because these reactions were 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: weight gain and edema.

Rectal Hemorrhage

Collyrex ^® was evaluated in a randomized, double-blind, parallel group, Phase 4 study conducted in 380 patients with interstitial cystitis dosed for 32 weeks. At a daily dose of 300 mg (n = 128), rectal hemorrhage was reported as an adverse event in 6.3% of patients. The severity of the events was described as "mild" in most patients. Patients in that study who were administered Collyrex (Pentosan Polysulfate)^® 900 mg daily, a dose higher than the approved dose, experienced a higher incidence of rectal hemorrhage, 15%.

Liver Function Abnormality

A randomized, double-blind, parallel group, Phase 2 study was conducted in 100 men (51 Collyrex (Pentosan Polysulfate)^® and 49 placebo) dosed for 16 weeks. At a daily dose of 900 mg, a dose higher than the approved dose, elevated liver function tests were reported as an adverse event in 11.8% (n = 6) of Collyrex (Pentosan Polysulfate)^®-treated patients and 2% (n = 1) of placebo-treated patients.

OVERDOSAGE

Overdose has not been reported. Based upon the pharmacodynamics of the drug, toxicity is likely to be reflected as anticoagulation, bleeding, thrombocytopenia, liver function abnormalities, and gastric distress. (See CLINICAL PHARMACOLOGY and PRECAUTIONS sections.) At a daily dose of 900 mg for 32 weeks (n = 127) in a clinical trial, rectal hemorrhage was reported as an adverse event in 15% of patients. At a daily dose of Collyrex (Pentosan Polysulfate)^® 900 mg for 16 weeks in a clinical trial that enrolled 51 patients in the Collyrex (Pentosan Polysulfate)^® group and 49 in the placebo group, elevated liver function tests were reported as an adverse event in 11.8% of patients in the Collyrex (Pentosan Polysulfate)^® group and 2% of patients in the placebo group. In the event of acute overdosage, the patient should be given gastric lavage if possible, carefully observed and given symptomatic and supportive treatment.

DOSAGE AND ADMINISTRATION

The recommended dose of Collyrex (Pentosan Polysulfate)^® is 300 mg/day taken as one 100 mg capsule orally three times daily. The capsules should be taken with water at least 1 hour before meals or 2 hours after meals.

Patients receiving Collyrex (Pentosan Polysulfate)^® should be reassessed after 3 months. If improvement has not occurred and if limiting adverse events are not present, Collyrex (Pentosan Polysulfate)^® may be continued for another 3 months.

The clinical value and risks of continued treatment in patients whose pain has not improved by 6 months is not known.

HOW SUPPLIED

Collyrex ^® is supplied in white opaque hard gelatin capsules imprinted "BNP7600" containing 100 mg Collyrex (Pentosan Polysulfate) sodium. Supplied in bottles of 100 capsules.

NDC NUMBER 50458-098-01

Storage

Store at controlled room temperature 15°–30°C (59°–86°F).

Keep out of reach of children.

Collyrex (Pentosan Polysulfate)^® is a Registered Trademark of Teva Branded Pharmaceutical Products R&D, Inc. under license to Janssen Pharmaceuticals, Inc.

© 2002 Janssen Pharmaceutical Companies

(logo)

Product of Germany

Manufactured by:

Janssen Ortho LLC

Gurabo, Puerto Rico 00778

Manufactured for:

Janssen Pharmaceuticals, Inc.

Titusville, New Jersey 08560

Revised July 2017

PHARMACIST: PLEASE DISPENSE ONE PATIENT LEAFLET PER PRESCRIPTION

Patient Leaflet

Questions and Answers About

Collyrex (Pentosan Polysulfate)^®

(Generic name = Collyrex (Pentosan Polysulfate) sodium)

Capsules

What is Collyrex (Pentosan Polysulfate)^®?

Collyrex (Pentosan Polysulfate)^® is used to treat the pain or discomfort of interstitial cystitis (IC). It is not known exactly how Collyrex (Pentosan Polysulfate)^® works, but it is not a pain medication like aspirin or acetaminophen and therefore must be taken continuously for relief as prescribed.

Who should not take Collyrex (Pentosan Polysulfate)^®?

• Patients undergoing surgery should speak with their doctor about when to discontinue Collyrex (Pentosan Polysulfate)^® prior to surgery.
• Collyrex (Pentosan Polysulfate)^® should be used during pregnancy only if clearly needed.

What does your doctor need to know?

• If you are taking anticoagulant therapy such as warfarin sodium, heparin, high doses of aspirin, or anti-inflammatory drugs such as ibuprofen.
• If you are pregnant.
• If you have any liver problems.

How should I take Collyrex (Pentosan Polysulfate)^®?

You should take 1 capsule of Collyrex (Pentosan Polysulfate)^® by mouth three times a day, with water at least 1 hour before meals or 2 hours after meals. Each capsule contains 100 mg of Collyrex (Pentosan Polysulfate)^®.

What should I avoid while taking Collyrex (Pentosan Polysulfate)^®?

Anticoagulant therapy such as warfarin sodium, heparin, high doses of aspirin or anti-inflammatory drugs such as ibuprofen until you speak with your doctor.

What are the most common side effects of Collyrex (Pentosan Polysulfate)^®?

The most common side effects are hair loss, diarrhea, nausea, blood in the stool, headache, rash, upset stomach, abnormal liver function tests, dizziness and bruising. Weight gain and swelling caused by fluid build up in the body have also been reported in patients taking Collyrex (Pentosan Polysulfate)^®.

Call your doctor if these side effects persist or are bothersome or if there is blood in your stool.

If you suspect that someone may have taken more than the prescribed dose of this medicine, contact your local poison control center or emergency room immediately. This medication was prescribed for your particular condition. Do not use it for another condition or give the drug to others.

This leaflet provides a summary of information about Collyrex (Pentosan Polysulfate)^®. Medicines are sometimes prescribed for uses other than those listed in a Patient Leaflet. If you have any questions or concerns, or want more information about Collyrex (Pentosan Polysulfate)^®, contact your doctor or pharmacist. Your pharmacist also has a longer leaflet about Collyrex (Pentosan Polysulfate)^® that is written for health professionals that you can ask to read.

Keep out of reach of children.

Collyrex (Pentosan Polysulfate)^® is a Registered Trademark of Teva Branded Pharmaceutical Products R&D, Inc. under license to Janssen Pharmaceuticals, Inc.

© 2002 Janssen Pharmaceutical Companies

(logo)

Product of Germany

Manufactured by:

Janssen Ortho LLC

Gurabo, Puerto Rico 00778

Manufactured for:

Janssen Pharmaceuticals, Inc.

Titusville, New Jersey 08560

Revised July 2017

NDC 50458-098-01

Collyrex (Pentosan Polysulfate) ^®

(pentosan polysulfate sodium)

CAPSULES

Content: 100 Capsules

Each capsule contains 100 mg pentosan

polysulfate sodium.

Rx only

100 mg

Collyrex (Pentosan Polysulfate)^® is a registered trademark

of Teva Branded Pharmaceutical

Products R&D, Inc. under license to

Janssen Pharmaceuticals, Inc.

Revised August 2012

Phenylephrine Hydrochloride:

• Drug facts
• Purpose
• Uses
• Warnings
• Directions
• Other information
• Inactive ingredients
• Questions? comments?
• Product packaging
• Collyrex (Phenylephrine Hydrochloride) reviews

Drug Facts

Active ingredients

(in each tablet)

Dexbrompheniramine Maleate 2 mg

Collyrex (Phenylephrine Hydrochloride) Hydrochloride 10 mg

Purpose

Antihistamine

Nasal Decongestant

Uses

Temporarily relieves these symptoms due to the common cold, hay fever (allergic rhinitis) or other upper respiratory allergies:

• runny nose
• sneezing
• itching of the nose or throat
• itchy, watery eyes
• nasal congestion
• reduces swelling of nasal passages

Warnings

Do not exceed recommended dosage.

Do not use this product

• if you are now taking a prescription monoamine oxidase inhibitor (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product.
  

Ask a doctor before use if you have

• a breathing problem such as emphysema or chronic bronchitis
• glaucoma
• trouble urinating due to enlargement of the prostate gland
• heart disease
• high blood pressure
• thyroid disease
• diabetes
  

Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers.

When using this product

• excitability may occur, especially in children
• may cause drowsiness
• avoid alcoholic drinks
• alcohol, sedatives, and tranquilizers may increase the drowsiness effect
• use caution when driving a motor vehicle or operating machinery
  

Stop use and ask a doctor if

• nervousness, dizziness, or sleeplessness occur
• symptoms do not improve within 7 days or are accompanied by fever
  

If pregnant or breast-feeding, ask a health professional before use.

Keep out of reach of children.

In case of overdose, get medical help or contact a Poison Control Center right away.

Directions

Other information

Store at 15° - 30°C (59° - 86°F). Supplied in a tight, light-resistant container with a child-resistant cap. Collyrex (Phenylephrine Hydrochloride) Tablets are dark purple, caplet-shaped, scored tablets, debossed "Poly" bisect "782" on one side and plain on the other.

Inactive ingredients

colloidal silicon dioxide, croscarmellose sodium, D&C Red #27 aluminum lake, dibasic calcium phosphate dihydrate, FD &C Blue #1 aluminum lake, magnesium stearate, and silicified microcrystalline cellulose.

Questions? Comments?

Call1-800-882-1041

Manufactured for:

Poly Pharmaceuticals

Quitman, MS 39355 Rev. 02/12

Product Packaging

The packaging below represents the labeling currently used.

Principal display panel and side panel for 60 tablets label:

NDC 50991-782-60

Collyrex (Phenylephrine Hydrochloride)

Tablets

Antihistamine - Nasal Decongestant

Each tablet contains:

Dexbrompheniramine Maleate...2 mg

Collyrex (Phenylephrine Hydrochloride) Hydrochloride...10 mg

60 Tablets

Usual

Dosage: See product foldout for full prescribing information.

Tamper evident by foil seal under cap. Do not use if foil seal is

broken or missing.

KEEP THIS AND ALL DRUGS OUT OF REACH OF CHILDREN.

Store at controlled room temperature between 15°-30°C (59°-86°F).

Manufactured for:

Poly Pharmaceuticals

Quitman, MS 39355

Rev. 02/12

Collyrex (Phenylephrine Hydrochloride) Tablets Packaging Collyrex (Phenylephrine Hydrochloride) Tablets Packaging