Tyvaso

Dosage Form: inhalation solution
FULL PRESCRIBING INFORMATION

Tyvaso® (treprostinil) inhalation solution

For Oral Inhalation Only

Indications and Usage for Tyvaso

Tyvaso is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).

The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.

While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration [see Clinical Studies (14)].

Tyvaso Dosage and Administration

Usual Dosage in Adults

Tyvaso is intended for oral inhalation using the Tyvaso Inhalation System, which consists of an ultrasonic, pulsed delivery device and its accessories.

Tyvaso is dosed in 4 separate, equally spaced treatment sessions per day, during waking hours. The treatment sessions should be approximately 4 hours apart.

Initial Dosage:

Therapy should begin with 3 breaths of Tyvaso (18 mcg of treprostinil), per treatment session, 4 times daily. If 3 breaths are not tolerated, reduce to 1 or 2 breaths and subsequently increase to 3 breaths, as tolerated.

Maintenance Dosage:

Dosage should be increased by an additional 3 breaths at approximately 1-2 week intervals, if tolerated, until the target dose of 9 breaths (54 mcg of treprostinil) is reached per treatment session, 4 times daily. If adverse effects preclude titration to target dose, Tyvaso should be continued at the highest tolerated dose.

If a scheduled treatment session is missed or interrupted, therapy should be resumed as soon as possible at the usual dose.

The maximum recommended dosage is 9 breaths per treatment session, 4 times daily.

Patients with Hepatic Insufficiency

Plasma clearance of treprostinil is reduced in patients with hepatic insufficiency. Patients with hepatic insufficiency may therefore be at increased risk of dose-dependent adverse reactions because of an increase in systemic exposure [see Warnings and Precautions (5.3), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Patients with Renal Insufficiency

Plasma clearance of treprostinil may be reduced in patients with renal insufficiency, since treprostinil and its metabolites are excreted mainly through the urinary route. Patients with renal insufficiency may therefore be at increased risk of dose-dependent adverse reactions [see Warnings and Precautions (5.3), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

Administration

Tyvaso must be used only with the Tyvaso Inhalation System. Patients should follow the instructions for use for operation of the Tyvaso Inhalation System and for daily cleaning of the device components after the last treatment session of the day. To avoid potential interruptions in drug delivery because of equipment malfunction, patients should have access to a back-up Tyvaso Inhalation System device.

Do not mix Tyvaso with other medications in the Tyvaso Inhalation System. Compatibility of Tyvaso with other medications has not been studied.

The Tyvaso Inhalation System should be prepared for use each day according to the instructions for use. One ampule of Tyvaso contains a sufficient volume of medication for all 4 treatment sessions in a single day. Prior to the first treatment session, the patient should twist the top off a single Tyvaso ampule and squeeze the entire contents into the medicine cup. Between each of the 4 daily treatment sessions, the device should be capped and stored upright with the remaining medication inside.

At the end of each day, the medicine cup and any remaining medication must be discarded. The device must be cleaned each day according to the instructions for use.

Avoid skin or eye contact with Tyvaso solution. Do not orally ingest the Tyvaso solution.

Dosage Forms and Strengths

Sterile solution for oral inhalation: 2.9 mL ampule containing 1.74 mg of treprostinil (0.6 mg per mL).

Contraindications

None.

Warnings and Precautions

Patients with Pulmonary Disease or Pulmonary Infections

The safety and efficacy of Tyvaso have not been established in patients with significant underlying lung disease (e.g., asthma or chronic obstructive pulmonary disease). Patients with acute pulmonary infections should be carefully monitored to detect any worsening of lung disease and loss of drug effect.

Risk of Symptomatic Hypotension

Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Tyvaso may produce symptomatic hypotension.

Patients with Hepatic or Renal Insufficiency

Titrate slowly in patients with hepatic or renal insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function [see Dosage and Administration (2.2, 2.3), Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)].

Risk of Bleeding

Since Tyvaso inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulant therapy.

Effect of Other Drugs on Treprostinil

Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness [see Drug Interactions (7.5) and Clinical Pharmacology (12.3)].

Adverse Reactions

The following potential adverse reactions are described in Warnings and Precautions (5):

-

Decrease in systemic blood pressure [see Warnings and Precautions (5.2)].

-

Bleeding [see Warnings and Precautions (5.4)].

Adverse Reactions Identified in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a 12-week placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most commonly reported adverse reactions on Tyvaso included: cough and throat irritation; headache, gastrointestinal effects, muscle, jaw or bone pain, flushing and syncope. Table 1 lists the adverse reactions that occurred at a rate of at least 4% and were more frequent in patients treated with Tyvaso than with placebo.

Table 1: Adverse Events in ≥ 4% of PAH Patients Receiving Tyvaso and More Frequent* than Placebo

Adverse Event	Treatment n (%)
	Tyvaso n = 115	Placebo n = 120
* More than 3% greater than placebo
Cough	62 (54)	35 (29)
Headache	47 (41)	27 (23)
Throat Irritation / Pharyngolaryngeal Pain	29 (25)	17 (14)
Nausea	22 (19)	13 (11)
Flushing	17 (15)	1 (<1)
Syncope	7 (6)	1 (<1)

The safety of Tyvaso was also studied in a long-term, open-label extension study in which 206 patients were dosed for a mean duration of one year. The adverse events during this chronic dosing study were qualitatively similar to those observed in the 12-week placebo controlled trial.

Adverse Events Associated with Route of Administration

Adverse events in the treated group during the double-blind and open-label phase reflecting irritation to the respiratory tract included: cough, throat irritation, pharyngeal pain, epistaxis, hemoptysis and wheezing. Serious adverse events during the open-label portion of the study included pneumonia in 8 subjects. There were three serious episodes of hemoptysis (one fatal) noted during the open-label experience.

Drug Interactions

Pharmacokinetic/pharmacodynamic interaction studies have not been conducted with inhaled treprostinil (Tyvaso); however, some of such studies have been conducted with orally (treprostinil diethanolamine) and subcutaneously administered treprostinil (Remodulin®).

Pharmacodynamics

Antihypertensive Agents or Other Vasodilators

Concomitant administration of Tyvaso with diuretics, antihypertensive agents or other vasodilators may increase the risk of symptomatic hypotension.

Anticoagulants

Since treprostinil inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulants.

Pharmacokinetics

Bosentan

In a human pharmacokinetic study conducted with bosentan (250 mg/day) and an oral formulation of treprostinil (treprostinil diethanolamine), no pharmacokinetic interactions between treprostinil and bosentan were observed.

Sildenafil

In a human pharmacokinetic study conducted with sildenafil (60 mg/day) and an oral formulation of treprostinil (treprostinil diethanolamine), no pharmacokinetic interactions between treprostinil and sildenafil were observed.

Effect of Cytochrome P450 Inhibitors and Inducers

In vitro studies of human hepatic microsomes showed that treprostinil does not inhibit cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A. Additionally, treprostinil does not induce cytochrome P450 isoenzymes CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A.

Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diethanolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor gemfibrozil increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer rifampin decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8 [see Warnings and Precautions (5.5)].

Effect of Other Drugs on Treprostinil

Drug interaction studies have been carried out with treprostinil (oral or subcutaneous) co-administered with acetaminophen (4 g/day), warfarin (25 mg/day), and fluconazole (200 mg/day), respectively in healthy volunteers. These studies did not show a clinically significant effect on the pharmacokinetics of treprostinil. Treprostinil does not affect the pharmacokinetics or pharmacodynamics of warfarin. The pharmacokinetics of R- and S- warfarin and the INR in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous infusion of treprostinil at an infusion rate of 10 ng/kg/min.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category B

There are no adequate and well controlled studies with Tyvaso in pregnant women. Animal reproduction studies have not been conducted with treprostinil administered by the inhalation route. However, studies in pregnant rabbits using continuous subcutaneous (sc) infusions of treprostinil sodium at infusion rates higher than the recommended human sc infusion rate resulted in an increased incidence of fetal skeletal variations associated with maternal toxicity [see Developmental Toxicity (13.3)]. Animal reproduction studies are not always predictive of human response; Tyvaso should be used during pregnancy only if clearly needed.

Labor and Delivery

No treprostinil treatment-related effects on labor and delivery were seen in animal studies. The effect of treprostinil on labor and delivery in humans is unknown.

Nursing Mothers

It is not known whether treprostinil is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when treprostinil is administered to nursing women.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Clinical studies of Tyvaso did not include patients younger than 18 years to determine whether they respond differently from older patients.

Geriatric Use

Clinical studies of Tyvaso did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.

Patients with Hepatic Insufficiency

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects with mild-to-moderate hepatic insufficiency. Uptitrate slowly when treating patients with hepatic insufficiency because of the risk of an increase in systemic exposure which may lead to an increase in dose-dependent adverse effects. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Clinical Pharmacology (12.3), Dosage and Administration (2.2) and Warnings and Precautions (5.3)].

Patients with Renal Insufficiency

No studies have been performed in patients with renal insufficiency. Since treprostinil and its metabolites are excreted mainly through the urinary route, patients with renal insufficiency may have decreased clearance of the drug and its metabolites and consequently, dose-related adverse outcomes may be more frequent [see Clinical Pharmacology (12.3), Dosage and Administration (2.3) and Warnings and Precautions (5.3)].

Overdosage

In general, symptoms of overdose with Tyvaso include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Provide general supportive care until the symptoms of overdose have resolved.

Tyvaso Description

Tyvaso is a sterile formulation of treprostinil intended for administration by oral inhalation using the Tyvaso Inhalation System. Tyvaso is supplied in 2.9 mL low density polyethylene (LDPE) ampules, containing 1.74 mg treprostinil (0.6 mg/mL). Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate, 0.58 mg sodium hydroxide, 11.7 mg 1 N hydrochloric acid, and water for injection. Sodium hydroxide and hydrochloric acid may be added to adjust pH between 6.0 and 7.2.

Treprostinil is (1R,2R,3aS,9aS) - [[2,3,3a,4,9,9a - hexahydro - 2 - hydroxy - 1 - [(3S) - 3 - hydroxyoctyl] - 1H - benz[f]inden - 5 - yl]oxy]acetic acid. Treprostinil has a molecular weight of 390.51 and a molecular formula of C23H34O5.

The structural formula of treprostinil is:

Tyvaso - Clinical Pharmacology

Mechanism of Action

Treprostinil is a prostacyclin analogue. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.

Pharmacodynamics

In a clinical trial of 240 healthy volunteers, single doses of Tyvaso 54 mcg (the target maintenance dose per session) and 84 mcg (supratherapeutic inhalation dose) prolonged the corrected QTc interval by approximately 10 ms. The QTc effect dissipated rapidly as the concentration of treprostinil decreased.

Pharmacokinetics

Pharmacokinetic information for single doses of inhaled treprostinil was obtained in healthy volunteers in three separate studies. Treprostinil systemic exposure (AUC and Cmax) post-inhalation was shown to be proportional to the doses administered (18 mcg – 90 mcg).

Absorption and Distribution

In a three-period crossover study, the bioavailability of two single doses of Tyvaso (18 mcg and 36 mcg) was compared with that of intravenous treprostinil in 18 healthy volunteers. Mean estimates of the absolute systemic bioavailability of treprostinil after inhalation were approximately 64% (18 mcg) and 72% (36 mcg).

Treprostinil plasma exposure data were obtained from two studies at the target maintenance dose, 54 mcg. The mean Cmax at the target dose was 0.91 and 1.32 ng/mL with corresponding mean Tmax of 0.25 and 0.12 hr, respectively. The mean AUC for the 54 mcg dose was 0.81 and 0.97 hr∙ng/mL, respectively.

Following parenteral infusion, the apparent steady state volume of distribution (Vss) of treprostinil is approximately 14 L/70 kg ideal body weight.

In vitro treprostinil is 91% bound to human plasma proteins over the 330-10,000 mcg/L concentration range.

Metabolism and Excretion

Of subcutaneously administered treprostinil, only 4% is excreted unchanged in urine. Treprostinil is substantially metabolized by the liver, primarily by CYP2C8. Metabolites are excreted in urine (79%) and feces (13%) over 10 days. Five apparently inactive metabolites were detected in the urine, each accounting for 10-15% of the dose administered. Four of the metabolites are products of oxidation of the 3-hydroxyloctyl side chain and one is a glucuroconjugated derivative (treprostinil glucuronide).

The elimination of treprostinil (following subcutaneous administration of treprostinil) is biphasic, with a terminal elimination half-life of approximately 4 hours using a two compartment model.

Special Populations

Hepatic Insufficiency

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects presenting with mild-to-moderate hepatic insufficiency. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Dosage and Administration (2.2), Warnings and Precautions (5.3) and Use in Specific Populations (8.6)].

Renal Insufficiency

No studies have been performed in patients with renal insufficiency; therefore, since treprostinil and its metabolites are excreted mainly through the urinary route, there is the potential for an increase in both parent drug and its metabolites and an increase in systemic exposure [see Dosage and Administration (2.3), Warnings and Precautions (5.3) and Use in Specific Populations (8.7)].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies have not been performed to evaluate the carcinogenic potential of treprostinil. In vitro and in vivo genetic toxicology studies did not demonstrate any mutagenic or clastogenic effects of treprostinil. Treprostinil sodium did not affect fertility or mating performance of male or female rats given continuous subcutaneous (sc) infusions at rates of up to 450 ng treprostinil/kg/min [about 59 times the recommended starting human sc infusion rate (1.25 ng/kg/min) and 8 times the average rate (9.3 ng/kg/min) achieved in clinical trials, on a ng/m2 basis]. In this study, males were dosed from 10 weeks prior to mating and through the 2-week mating period. Females were dosed from 2 weeks prior to mating until gestational day 6.

Developmental Toxicity

In pregnant rats, continuous sc infusions of treprostinil sodium during organogenesis and late gestational development, at rates as high as 900 ng treprostinil/kg/min (about 117 times the recommended starting human sc infusion rate and about 16 times the average rate achieved in clinical trials, on a ng/m2 basis), resulted in no evidence of harm to the fetus. In pregnant rabbits, effects of continuous sc infusions of treprostinil during organogenesis were limited to an increased incidence of fetal skeletal variations (bilateral full rib or right rudimentary rib on lumbar vertebra 1) associated with maternal toxicity (reduction in body weight and food consumption) at an infusion rate of 150 ng treprostinil/kg/min (about 41 times the starting human sc infusion rate and 5 times the average rate achieved in clinical trials, on a ng/m2 basis).

Inhalational Toxicity

Rats and dogs that received daily administrations of treprostinil by inhalation for 3 months developed respiratory tract lesions (respiratory epithelial degeneration, goblet cell hyperplasia/hypertrophy, epithelial ulceration, squamous epithelial degeneration and necrosis, and lung hemorrhage). Some of the same lesions seen in animals sacrificed at the end of treatment (larynx, lung and nasal cavity lesions in rats, and lesions of the larynx in dogs) were also observed in animals sacrificed after a 4-week recovery period. Rats also developed cardiac changes (degeneration/fibrosis). A no-effect dose level for these effects was not demonstrated in rats (doses as low as 7 µg/kg/day were administered); whereas 107 µg/kg/day was a no-effect dose level in dogs.

Clinical Studies

TRIUMPH I, was a 12-week, randomized, double-blind, placebo-controlled multi-center study of patients with PAH. The study population included 235 clinically stable subjects with pulmonary arterial hypertension (WHO Group 1), nearly all with NYHA Class III (98%) symptoms who were receiving either bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase-5 inhibitor) for at least three months prior to study initiation. Concomitant therapy also could have included anticoagulants, other vasodilators (e.g., calcium channel blockers), diuretics, oxygen, and digitalis, but not a prostacyclin. These patients were administered either placebo or Tyvaso in four daily treatment sessions with a target dose of 9 breaths (54 mcg) per session over the course of the 12-week study. Patients were predominantly female (82%), had the origin of PAH as idiopathic/heritable (56%), secondary to connective tissue diseases (33%) or secondary to HIV or previous use of anorexigens (12%); bosentan was the concomitant oral medication in 70% of those enrolled, sildenafil in 30%.

The primary efficacy endpoint of the trial was the change in six-minute walk distance (6MWD) relative to baseline at 12 weeks. 6MWD was measured at peak exposure (between 10 and 60 minutes after dosing), and 3-5 hours after bosentan or 0.5-2 hours after sildenafil. Patients receiving Tyvaso had a placebo-corrected median change from baseline in peak 6MWD of 20 meters at Week 12 (p<0.001). The distribution of these 6MWD changes from baseline at Week 12 were plotted across the range of observed values (Figure 1). 6MWD measured at trough exposure (defined as measurement of 6MWD at least 4 hours after dosing) improved by 14 meters. There were no placebo-controlled 6MWD assessments made after 12 weeks.

Figure 1: Distributions of 6MWD Changes from Baseline at Week 12 during Peak Plasma Concentration of Tyvaso

The placebo-corrected median treatment effect on 6MWD was estimated (using the Hodges-Lehmann estimator) within various subpopulations defined by age quartile, gender, geographic region of the study site, disease etiology, baseline 6MWD quartile, and type of background therapy (Figure 2).

Figure 2. Placebo Corrected Median Treatment Effect (Hodges-Lehmann estimate with 95% CI) on 6MWD Change from Baseline at Week 12 During Peak Plasma Concentration of Tyvaso for Various Subgroups

How Supplied/Storage and Handling

Tyvaso (treprostinil) inhalation solution is supplied in 2.9 mL clear LDPE ampules packaged as four ampules in a foil pouch. Tyvaso is a clear colorless to slightly yellow solution containing 1.74 mg treprostinil per ampule at a concentration of 0.6 mg/mL.

Ampules of Tyvaso are stable until the date indicated when stored in the unopened foil pouch at 25°C (77°F), with excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the foil pack is opened, ampules should be used within 7 days. Because Tyvaso is light-sensitive, unopened ampules should be stored in the foil pouch.

One ampule of Tyvaso should be used each day in the Tyvaso Inhalation System. After a Tyvaso ampule is opened and transferred to the medicine cup, the solution should remain in the device for no more than one day (24 hours). Any remaining solution should be discarded at the end of the day.

Tyvaso Inhalation System Starter Kit containing a 28 ampule carton of Tyvaso [seven foil pouches each containing four 2.9 mL ampules. Each ampule contains 1.74 mg treprostinil (0.6 mg per mL)] and the Tyvaso Inhalation System. (NDC 66302-206-01)

Tyvaso Inhalation System Refill Kit containing a 28 ampule carton of Tyvaso [seven foil pouches each containing four 2.9 mL ampules. Each ampule contains 1.74 mg treprostinil (0.6 mg per mL)] and accessories. (NDC 66302-206-02)

Tyvaso 4 Pack Carton with one foil pouch containing four 2.9 mL ampules. Each ampule contains 1.74 mg treprostinil (0.6 mg per mL). (NDC 66302-206-03).

Patient Counseling Information

Patients should be properly trained in the administration process for Tyvaso, including dosing, Tyvaso Inhalation System set up, operation, cleaning, and maintenance, according to the instructions for use [see Dosage and Administration (2.1)].

To avoid potential interruptions in drug delivery because of equipment malfunction, patients should have access to a back-up Tyvaso Inhalation System device [see Dosage and Administration (2.4)].

In the event that a scheduled treatment session is missed or interrupted, therapy should be resumed as soon as possible [see Dosage and Administration (2.1)].

Patients should avoid skin or eye contact with Tyvaso. If Tyvaso comes in contact with the skin or eyes, instruct patients to rinse immediately with water [see Dosage and Administration (2.4)].

US Patent No. 5,153,222

US Patent No. 6,765,117

US Patent No. 6,521,212

US Patent No. 6,756,033

©Copyright 2011 United Therapeutics Corp. All rights reserved.

Tyvaso manufactured for:

United Therapeutics Corp.

Research Triangle Park, NC 27709

PATIENT PACKAGE INSERT

Tyvaso (Tī-vāsō)

(treprostinil)

Inhalation Solution

Read this Patient Package Insert before you start taking Tyvaso and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is Tyvaso?

Tyvaso is a prescription medicine used in adults to treat pulmonary arterial hypertension (PAH), which is high blood pressure in the arteries of your lungs. Tyvaso can improve the ability to do exercise in people who also take bosentan (an endothelin receptor antagonist (ERA)) or sildenafil (a phosphodiesterase-5 (PDE-5) inhibitor). Your ability to do exercise decreases 4 hours after taking Tyvaso.

It is not known if Tyvaso is safe or effective in people under 18 years of age.

What should I tell my healthcare provider before taking Tyvaso?

Before taking Tyvaso, tell your healthcare provider about all of your medical conditions, including if you:

• have lung disease, such as asthma or chronic obstructive pulmonary disease (COPD)


• have a lung infection


• have liver problems or kidney problems


• have low blood pressure


• are pregnant or plan to become pregnant. It is not known if Tyvaso will harm your unborn baby. Women who can become pregnant should use effective birth control while taking Tyvaso.


• are breast-feeding or plan to breast-feed. It is not known if Tyvaso passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking Tyvaso.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Tyvaso and other medicines may affect each other.

Especially tell your healthcare provider if you take any of these medicines:

• medicines that decrease blood clotting


• water pills (diuretics)


• medicines used to treat high blood pressure or heart disease


• gemfibrozil (Lopid) (for high cholesterol)


• rifampin (Rimactane, Rifadin, Rifamate, Rifater) (for infection)

Know the medicines you take. Keep a list of them and show it to your healthcare provider and specialty pharmacist when you get a new medicine.

How should I take Tyvaso?

• Take Tyvaso each day exactly as your healthcare provider tells you.


• See the detailed Tyvaso Inhalation System Instructions for Use.


• Tyvaso is breathed in (inhaled) through your mouth into your lungs. Tyvaso should only be used with the Tyvaso Inhalation System.


• Tyvaso is taken in 4 treatment sessions each day during waking hours. The sessions should be at about 4 hours apart.


• At the beginning of each day, it will take about 5 minutes to prepare the Tyvaso Inhalation System. Each treatment session will take 2 to 3 minutes.


• Take your first Tyvaso treatment session in the morning and take your last treatment session before bedtime.


• Your healthcare provider may change your dose if needed.


• If you miss a dose of Tyvaso take it as soon as you remember.


• Do not let Tyvaso solution get into your eyes or onto your skin. If it does, rinse your skin or eyes right away with water.

What are the possible side effects of Tyvaso?

Tyvaso can cause serious side effects, including:

• Tyvaso may increase the risk of bleeding in people who take blood thinners (anticoagulants).


• If you have low blood pressure, Tyvaso may lower your blood pressure further.

Ask your healthcare provider if you are not sure if this applies to you.

The most common side effects of Tyvaso include:

• coughing


• headache


• nausea


• reddening of your face and neck (flushing)


• throat irritation and pain


• fainting or loss of consciousness

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Tyvaso. For more information, ask your healthcare provider or specialty pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Tyvaso?

• Store Tyvaso ampules in the unopened foil pack between 59°F to 86°F (15°C to 30°C) until ready to use.


• When the foil pouch is opened, Tyvaso ampules should be used within 7 days.


• Tyvaso is sensitive to light. The unopened Tyvaso ampules should be stored in the foil pouch.


• After a Tyvaso ampule is opened and put into the medicine cup in the Tyvaso Inhalation System, Tyvaso can be kept in the medicine cup for no more than 1 day (24 hours).


• Tyvaso that is left in the medicine cup at the end of the day must be thrown away.

Keep Tyvaso and all medicines out of the reach of children.

General information about the safe and effective use of Tyvaso.

Medicines are sometimes prescribed for conditions that are not mentioned in a patient information leaflet. Do not use Tyvaso for a condition for which it was not prescribed. Do not give Tyvaso to other people, even if they have the same symptoms you have. It may harm them.

This patient information leaflet summarizes the most important information about Tyvaso. You can ask your healthcare provider or specialty pharmacist for information about Tyvaso that is written for health professionals.

For more information, go to www.Tyvaso.com or call 1-866-458-6479.

What are the ingredients in Tyvaso?

Active ingredient: treprostinil

Inactive ingredients: sodium chloride, sodium citrate, sodium hydroxide, hydrochloric acid, and water for injection.

Tyvaso is a trademark of United Therapeutics Corporation.

Literature issued February 2011

United Therapeutics Corp.

Research Triangle Park, NC 27709 USA

Copyright © 2011, United Therapeutics Corp. All rights reserved.

PRINCIPAL DISPLAY PANEL - 4 Ampule Carton

Tyvaso®

(treprostinil)

INHALATION

SOLUTION

Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL)

Four 2.9 mL ampules

For oral inhalation use only

See package insert and

Instructions For Use manual

for dosage and administration

PRINCIPAL DISPLAY PANEL - 28 Ampule Carton

Tyvaso®

(treprostinil)

INHALATION

SOLUTION

Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL)

Seven foil pouches each containing four

2.9 mL ampules

For oral inhalation use only

See package insert and

Instructions For Use manual

for dosage and administration.

PRINCIPAL DISPLAY PANEL - Starter Kit

Tyvaso®

(treprostinil)

INHALATION

SOLUTION

Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL)

Tyvaso is for oral inhalation use only and is intended for administration with the Tyvaso Inhalation System

See package insert and Instructions for Use manual for dosage and administration

Tyvaso Inhalation System Starter Kit

CONTENTS	QTY	CONTENTS	QTY
28 ampule carton of Tyvaso (seven foil pouches each containing four 2.9 mL ampules)	1	Measuring cup	1
		Nose clip (for optional use)	1
Tyvaso Inhalation System Instructions for Use manual	1	Plugs for storage between treatment sessions	2
Tyvaso Inhalation System warranty card	1	AC wall plugs	2
Tyvaso Inhalation Device	2	Rechargeable battery	1
Sets of dome assembly, inhalation piece, mouthpiece, and 2 filter shells	2	12V DC car adapter	1
Medicine cups	32	Storage box	1
Filters	65	Carrying case	1

Each ampule of Tyvaso contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride,

18.3 mg sodium citrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection.

Hydrochloric acid and sodium hydroxide may have been added to adjust pH.

—

One new ampule should be used each day. Each ampule of Tyvaso (once opened and transferred to

the medicine cup) should remain in the device for no more than 1 day. Any remaining Tyvaso and the

medicine cup should be discarded at the end of each day

—

Once a foil pouch is opened, use ampules within 7 days

—

Store unused ampules of Tyvaso in the foil pouch until use, protected from light

—

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)

[see USP Controlled Room Temperature]

Keep out of the reach of children.

NDC 66302-206-01

Rx only

Manufactured for United Therapeutics Corporation

Research Triangle Park, NC 27709

Jointly marketed by

LUNGRX®

A breath of fresh thinking

United

Therapeutics

CORPORATION

EXP

LOT

Rev.01

PRINCIPAL DISPLAY PANEL - Refill Kit

Tyvaso®

(treprostinil)

INHALATION

SOLUTION

Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL)

Tyvaso is for oral inhalation use only and is intended for administration with the Tyvaso Inhalation System

See package insert and Instructions for Use manual for dosage and administration

Tyvaso Inhalation System Refill Kit

CONTENTS	QTY
28 ampule carton of Tyvaso (seven foil pouches each containing four 2.9 mL ampules)	1
Set of dome assembly, inhalation piece, mouthpiece, and 2 filter shells	1
Medicine cups	32
Filters	65
Plugs for storage between treatment sessions	2

Each ampule of Tyvaso contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride,

18.3 mg sodium citrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection.

Hydrochloric acid and sodium hydroxide may have been added to adjust pH.

—

One new ampule should be used each day. Each ampule of Tyvaso (once opened and transferred to

the medicine cup) should remain in the device for no more than 1 day. Any remaining Tyvaso and the

medicine cup should be discarded at the end of each day

—

Once a foil pouch is opened, use ampules within 7 days

—

Store unused ampules of Tyvaso in the foil pouch until use, protected from light

—

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)

[see USP Controlled Room Temperature]

Keep out of the reach of children.

NDC 66302-206-02

Rx only

Manufactured for United Therapeutics Corporation

Research Triangle Park, NC 27709

Jointly marketed by

LUNGRX®

A breath of fresh thinking

United

Therapeutics

CORPORATION

EXP

LOT

Rev.01

Tyvaso  treprostinil  inhalant

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 66302-206 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength treprostinil (treprostinil) treprostinil 1.74 mg  in 2.9 mL

Inactive Ingredients Ingredient Name Strength sodium chloride 18.9 mg  in 2.9 mL sodium citrate 18.3 mg  in 2.9 mL sodium hydroxide 0.6 mg  in 2.9 mL hydrochloric acid 11.7 mg  in 2.9 mL water

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 66302-206-01 1 BOX In 1 KIT contains a BOX 1 28 AMPULE In 1 BOX This package is contained within the KIT (66302-206-01) and contains a AMPULE 1 2.9 mL In 1 AMPULE This package is contained within a BOX and a KIT (66302-206-01) 2 66302-206-02 1 BOX In 1 KIT contains a BOX 2 28 AMPULE In 1 BOX This package is contained within the KIT (66302-206-02) and contains a AMPULE 2 2.9 mL In 1 AMPULE This package is contained within a BOX and a KIT (66302-206-02) 3 66302-206-03 4 AMPULE In 1 BOX contains a AMPULE 3 2.9 mL In 1 AMPULE This package is contained within the BOX (66302-206-03)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date

Intravenous nutritional products

A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes.

Intravenous nutritional products are also called parenteral nutrition. They supplement oral food intake. Partial parenteral nutrition provides only part of the patient

See also

Medical conditions associated with intravenous nutritional products:

• Fluid Retention
• Total Parenteral Nutrition

Drug List:

Aminosyn

Aminosyn-Hbc

Aminosyn-Hf

Aminosyn-Rf

Branchamin

Dextrose-And-Ringer-S

Extraneal-Lvp-Solution

Freamine-Hbc

Freamine-Iii

Hepatamine

Hyperlyte-Cr

Intralipid

Isolyte-S

Isolyte-S-Ph-7-4

Liposyn-Ii

Normosol-R

Plasma-Lyte-56

Plasma-Lyte-148

Premasol

Procalamine

Prosol

Renamin

Tpn-Electrolytes

Trophamine

Panretin

Pronunciation: a-li-TREH-tih-no-in
Generic Name: Alitretinoin
Brand Name: Panretin

Panretin is used for:

Treating skin sores/lesions in patients with AIDS-related Kaposi sarcoma. It may also be used to treat other conditions as determined by your doctor.

Panretin is a retinoid. It slows the growth of abnormal and normal skin cells. This slows or stops the growth of Kaposi sarcoma.

Do NOT use Panretin if:

• you are allergic to any ingredient in Panretin or to other retinoid medicines

Contact your doctor or health care provider right away if any of this applies to you.

Before using Panretin:

Tell your health care provider if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have increased white blood cell counts, eczema, or lymphoma

Some MEDICINES MAY INTERACT with Panretin. Tell your health care provider if you are taking any of the following medicines.

• Tranexamic acid because side effects may be increased by Panretin.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Panretin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Panretin:

Use Panretin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Panretin. Talk to your pharmacist if you have questions about this information.


• Wash and completely dry the affected area.


• Apply medicine generously to cover the lesion. Allow 3 to 5 minutes to dry before covering with clothing. Do not get Panretin on healthy skin surrounding the lesion.


• Wash your hands immediately after using Panretin, unless your hands are part of the treated area.


• Do not bandage or wrap the affected area.


• If you miss a dose of Panretin, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Panretin.

Important safety information:

• Panretin is for external use only. Do not get it in your eyes, on the inside of your nose or mouth, or near the vagina, tip of the penis, or rectum. If you get it in your eyes, rinse right away with cool water.


• Do not apply Panretin to normal skin surrounding the lesions as it may cause serious irritation to this skin.


• It may take 4 to 8 weeks or longer for Panretin to work. Do not stop using Panretin without checking with your doctor.


• Talk with your doctor before you use any other medicines or cleansers on your skin. Do NOT use insect repellants containing DEET.


• Do not shower, swim, or bathe for at least 3 hours after applying Panretin.


• You may use mineral oil between applications to help prevent dryness or itching. Do not apply mineral oil within 2 hours before or after applying Panretin.


• If severe irritation occurs, contact your doctor. You may need to temporarily stop using Panretin for a few days until the irritation stops.


• Panretin may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Panretin. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.


• Panretin contains alcohol. Do not store or use near open flames.


• Panretin should not be used in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Panretin has been shown to cause harm to the fetus. Do not become pregnant while you are using it. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Panretin while you are pregnant. It is not known if Panretin is found in breast milk. Do not breast-feed while using Panretin.

Possible side effects of Panretin:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Burning; flaking; itching; pain; peeling; rash; redness; scaling; skin inflammation; skin irritation; stinging; tingling.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blistering; cracking; crusting; draining; excessive pain; oozing; scabbing of the skin; swelling.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Panretin side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Panretin may be harmful if swallowed.

Proper storage of Panretin:

Store Panretin at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Panretin out of the reach of children and away from pets.

General information:

• If you have any questions about Panretin, please talk with your doctor, pharmacist, or other health care provider.


• Panretin is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Panretin. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Panretin resources

• Panretin Side Effects (in more detail)
• Panretin Use in Pregnancy & Breastfeeding
• Panretin Drug Interactions
• Panretin Support Group
• 0 Reviews for Panretin - Add your own review/rating

• Panretin Prescribing Information (FDA)


• Panretin Concise Consumer Information (Cerner Multum)


• Panretin Monograph (AHFS DI)


• Panretin Topical Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Panretin with other medications

• Kaposi's Sarcoma

HMS

medrysone

Dosage Form: Ophthalmic Suspension 1%

Sterile

HMS Description

HMS® (medrysone ophthalmic suspension) 1% is a topical anti-inflammatory agent for ophthalmic use.

Chemical Name:

11β-hydroxy-6α-methylpregn-4-ene-3,20-dione

Structural Formula:

Contains: Active: Medrysone 1%. Preservative: benzalkonium chloride 0.004%.

Inactives: edetate disodium; hypromellose; polyvinyl alcohol 1.4%; potassium chloride; purified water; sodium chloride; sodium phosphate, dibasic; sodium phosphate, monobasic; and sodium hydroxide to adjust the pH (6.2 - 7.5).

HMS - Clinical Pharmacology

HMS® (medrysone ophthalmic suspension) is a synthetic corticosteroid with topical anti-inflammatory activity. Glucocorticoids inhibit the edema, fibrin deposition, capillary dilation and phagocytic migration of the acute inflammatory response as well as capillary proliferation, deposition of collagen, and scar formation. HMS® (medrysone ophthalmic suspension) has less anti-inflammatory potency than 0.1% dexamethasone.

Indications and Usage for HMS

HMS® (medrysone ophthalmic suspension) is indicated for the treatment of allergic conjunctivitis, vernal conjunctivitis, episcleritis, and epinephrine sensitivity.

Contraindications

HMS® suspension is contraindicated in most viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. HMS® suspension is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids.

Warnings

HMS® (medrysone ophthalmic suspension) is not recommended for use in iritis and uveitis as its therapeutic effectiveness has not been demonstrated in these conditions.

Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Prolonged use may also suppress the host immune response and thus increase the hazard of secondary ocular infections.

Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation.

Acute purulent infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication.

If this product is used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients.

Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be checked frequently.

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.

Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is recommended.

Corticosteroids are not effective in mustard gas keratitis and Sjögren's keratoconjunctivitis.

Precautions

General:

The initial prescription and renewal of the medication order beyond 20 milliliters of HMS® suspension should be made by a physician only after examination of the patient with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. If signs and symptoms fail to improve after two days, the patient should be re-evaluated.

As fungal infections of the cornea are particularly prone to develop coincidentally with long-term local corticosteroid applications, fungal invasion should be suspected in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.

If this product is used for 10 days or longer, intraocular pressure should be monitored (see WARNINGS).

Information for Patients:

If inflammation or pain persists longer than 48 hours or becomes aggravated, the patient should be advised to discontinue use of the medication and consult a physician.

This product is sterile when packaged. To prevent contamination, care should be taken to avoid touching the bottle tip to eyelids or to any other surface. The use of this bottle by more than one person may spread infection. Keep bottle tightly closed when not in use. Keep out of the reach of children.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

No studies have been conducted in animals or in humans to evaluate the potential of these effects.

Pregnancy:

Teratogenic effects. Pregnancy Category C. Medrysone has been shown to be embryocidal in rabbits when given in doses 10 and 30 times the human ocular dose. Two drops of medrysone were applied to both eyes of pregnant rabbits 4 times per day on day 6 through 18 of gestation. A significant increase in early resorptions was observed in the treated rabbits. There are no adequate and well-controlled studies of medrysone in pregnant women. Medrysone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers:

It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human breast milk. Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from medrysone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use:

Safety and effectiveness in pediatric patients below the age of 3 years have not been established.

Geriatric Use:

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Adverse Reactions

Adverse reactions include, in decreasing order of frequency, elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage, posterior subcapsular cataract formation, and delayed wound healing.

Although systemic effects are extremely uncommon, there have been rare occurrences of systemic hypercorticoidism after use of topical steroids.

Corticosteroid-containing preparations have also been reported to cause acute anterior uveitis and perforation of the globe. Keratitis, conjunctivitis, corneal ulcers, mydriasis, conjunctival hyperemia, loss of accommodation and ptosis have occasionally been reported following local use of corticosteroids.

The development of secondary ocular infection (bacterial, fungal and viral) has occurred. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroids. The possibility of fungal invasion should be considered in any persistent corneal ulceration where steroid treatment has been used (see WARNINGS).

Transient burning and stinging upon instillation and other minor symptoms of ocular irritation have been reported with the use of HMS® suspension. Other adverse events reported with the use of HMS® suspension include: allergic reactions, foreign body sensation, and visual disturbance (blurry vision).

Overdosage

Overdosage will not ordinarily cause acute problems. If accidentally ingested, drink fluids to dilute.

HMS Dosage and Administration

Shake well before using. Instill one drop into the conjunctival sac up to every four hours.

How is HMS Supplied

HMS® (medrysone ophthalmic suspension) 1% is supplied sterile in opaque white LDPE plastic bottles with droppers with white high impact polystyrene (HIPS) caps as follows:

5 mL in 10 mL bottle -	NDC 11980-074-05
10 mL in 15 mL bottle -	NDC 11980-074-10

Note: Store at temperatures up to 25°C (77°F). Protect from freezing.

Rx Only

Revised August 2004

© 2004 Allergan, Inc.

Irvine, CA 92612, U.S.A.

6089X

® Marks owned by Allergan, Inc.

71741US11P

HMS  medrysone  suspension

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 11980-074 Route of Administration OPHTHALMIC DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Medrysone (Medrysone) Active 10 MILLIGRAM  In 1 MILLILITER edetate disodium Inactive   hypromellose Inactive   polyvinyl alcohol Inactive   potassium chloride Inactive   water Inactive   sodium chloride Inactive   sodium phosphate, dibasic Inactive   sodium phosphate, monobasic Inactive   sodium hydroxide Inactive   benzalkonium chloride Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 11980-074-05 5 mL (MILLILITER) In 1 BOTTLE None 2 11980-074-10 10 mL (MILLILITER) In 1 BOTTLE None

Revised: 02/2006Allergan, Inc.

More HMS resources

• HMS Side Effects (in more detail)
• HMS Dosage
• HMS Use in Pregnancy & Breastfeeding
• HMS Drug Interactions
• 0 Reviews for HMS - Add your own review/rating

• HMS Concise Consumer Information (Cerner Multum)

Compare HMS with other medications

• Postoperative Ocular Inflammation

Humibid LA

Pronunciation: gwye-FEN-eh-sin/poe-TASS-ee-um gwye-a-kole-SUL-foe-nate
Generic Name: Guaifenesin/Potassium Guaiacolsulfonate
Brand Name: Allfen and Humibid LA

Humibid LA is used for:

Relieving symptoms of cough and mucus in the chest due to respiratory infections, asthma, colds, or hay fever. It may also be used for other conditions as determined by your doctor.

Humibid LA is a combination of 2 expectorants. It works by thinning mucus (phlegm) in the lungs and making it less sticky and easier to cough up. This reduces chest congestion by making coughs more productive.

Do NOT use Humibid LA if:

• you are allergic to any ingredient in Humibid LA

Contact your doctor or health care provider right away if any of these apply to you.

Before using Humibid LA:

Some medical conditions may interact with Humibid LA. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a chronic cough that occurs with smoking, asthma, chronic bronchitis, or emphysema, or if cough occurs with large amounts of mucus

Some MEDICINES MAY INTERACT with Humibid LA. Tell your health care provider if you are taking any other medicines. However, no specific interactions with Humibid LA are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Humibid LA may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Humibid LA:

Use Humibid LA as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Humibid LA may be taken with or without food.


• Drinking extra fluids while you are taking Humibid LA is recommended. Check with your doctor for instructions.


• Swallow Humibid LA whole. Do not break, crush, or chew before swallowing.


• If you miss a dose of Humibid LA and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Humibid LA.

Important safety information:

• Humibid LA may cause dizziness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Humibid LA. Using Humibid LA alone, with certain other medicines, or with alcohol may lessen your ability to drive or to perform other potentially dangerous tasks.


• If cough persists for more than 1 week or is accompanied by a fever, contact your health care provider. A persistent cough could be a sign of a serious condition.


• Humibid LA may interfere with some lab tests. Make sure your doctor and lab personnel know you are taking Humibid LA.


• Use Humibid LA with extreme caution in CHILDREN younger than 12 years of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Humibid LA during pregnancy. It is unknown if Humibid LA is excreted in breast milk. If you are or will be breast-feeding while you are using Humibid LA, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Humibid LA:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Dizziness; headache; nausea; upset stomach; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); lower back or side pain.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch .

See also: Humibid LA side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Humibid LA:

Store Humibid LA at room temperature between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Humibid LA out of the reach of children and away from pets.

General information:

• If you have any questions about Humibid LA, please talk with your doctor, pharmacist, or other health care provider.


• Humibid LA is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Humibid LA. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Humibid LA resources

• Humibid LA Side Effects (in more detail)
• Humibid LA Use in Pregnancy & Breastfeeding
• Humibid LA Drug Interactions
• Humibid LA Support Group
• 0 Reviews for Humibid LA - Add your own review/rating

Compare Humibid LA with other medications

• Cough

Systemic Fungal Infection Medications

Drugs associated with Systemic Fungal Infection

The following drugs and medications are in some way related to, or used in the treatment of Systemic Fungal Infection. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Topics under Systemic Fungal Infection

• Aspergillosis (15 drugs in 5 topics)

• Blastomycosis (9 drugs)

• Fungal Endocarditis (4 drugs)

• Fungal Meningitis (21 drugs in 5 topics)

• Fungal Peritonitis (1 drug)

• Fungal Pneumonia (2 drugs)

• Fusariosis (1 drug)

• Gastrointestinal Candidiasis (15 drugs in 2 topics)

Drug List:

Ancobon

Vfend

Heparin sodium 1,000 I.U. / ml Solution for injection or concentrate for solution for infusion (without preservative)

1. Name Of The Medicinal Product

Monoparin 1,000 I.U./ml Solution for injection or concentrate for solution for infusion or Heparin sodium 1,000 I.U./ml Solution for injection or concentrate for solution for infusion

2. Qualitative And Quantitative Composition

Heparin sodium 1,000 I.U./ml (1,000 I.U./ml in 1ml, 5,000 I.U. in 5ml, 10,000 I.U in 10ml and 20,000 I.U in 20ml)

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Solution for injection or concentrate for solution for infusion

A colourless or straw-coloured liquid, free from turbidity and from matter that deposits on standing.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of deep vein thrombosis, pulmonary embolism, unstable angina pectoris and acute peripheral arterial occlusion.

In extracorporeal circulation and haemodialysis.

4.2 Posology And Method Of Administration

Route of administration

By continuous intravenous infusion in 5% glucose or 0.9% sodium chloride or by intermittent intravenous injection.

As the effects of heparin are short-lived, administration by intravenous infusion is preferable to intermittent intravenous injections.

Recommended dosage

Treatment of deep vein thrombosis, pulmonary embolism, unstable angina pectoris, acute peripheral arterial occlusion:

Adults:

Loading dose:	5,000 units intravenously (10,000 units may be required in severe pulmonary embolism)
Maintenance:	1,000-2,000 units/hour by intravenous infusion, or 5,000-10,000 units 4-hourly by intravenous injection.

Elderly:

Dosage reduction may be advisable.

Children and small adults:

Loading dose:	50 units/kg intravenously
Maintenance:	15-25 units/kg/hour by intravenous infusion, or 100 units/kg 4-hourly by intravenous injection

Daily laboratory monitoring (ideally at the same time each day, starting 4-6 hours after initiation of treatment) is essential during full-dose heparin treatment, with adjustment of dosage to maintain an APTT value 1.5-2.5 x midpoint of normal range or control value.

In extracorporeal circulation and haemodialysis

Adults:

Cardiopulmonary bypass:

Initially 300 units/kg intravenously, adjusted thereafter to maintain the activated clotting time (ACT) in the range 400-500 seconds.

Haemodialysis and haemofiltration:

Initially 1,000-5,000 units,

Maintenance: 1,000-2,000 units/hour, adjusted to maintain clotting time>40 minutes.

Heparin resistance

Patients with altered heparin responsiveness or heparin resistance may require disproportionately higher doses of heparin to achieve the desired effect. Also refer to section 4.4, Special warnings and precautions for use.

4.3 Contraindications

Patients who consume large amounts of alcohol, who are sensitive to the drug, who are actively bleeding or who have haemophilia or other bleeding disorders, severe liver disease (including oesophageal varices), purpura, severe hypertension, active tuberculosis or increased capillary permeability.

Patients with present or previous thrombocytopenia. The rare occurrence of skin necrosis in patients receiving heparin contra-indicates the further use of heparin either by subcutaneous or intravenous routes because of the risk of thrombocytopenia. Because of the special hazard of post-operative haemorrhage heparin is contra-indicated during surgery of the brain, spinal cord and eye, in procedures at sites where there is a risk of bleeding, in patients that have had recent surgery, and in patients undergoing lumbar puncture or regional anaesthetic block.

The relative risks and benefits of heparin should be carefully assessed in patients with a bleeding tendency or those patients with an actual or potential bleeding site eg. hiatus hernia, peptic ulcer, neoplasm, bacterial endocarditis, retinopathy, bleeding haemorrhoids, suspected intracranial haemorrhage, cerebral thrombosis or threatened abortion.

Menstruation is not a contra-indication.

4.4 Special Warnings And Precautions For Use

Platelet counts should be measured in patients receiving heparin treatment for longer than 5 days and the treatment should be stopped immediately in those who develop thrombocytopenia.

In patients with advanced renal or hepatic disease, a reduction in dosage may be necessary. The risk of bleeding is increased with severe renal impairment and in the elderly (particularly elderly women).

Although heparin hypersensitivity is rare, it is advisable to give a trial dose of 1,000 I.U. in patients with a history of allergy. Caution should be exercised in patients with known hypersensitivity to low molecular weight heparins.

In most patients, the recommended low-dose regimen produces no alteration in clotting time. However, patients show an individual response to heparin, and it is therefore essential that the effect of therapy on coagulation time should be monitored in patients undergoing major surgery.

Caution is recommended in spinal or epidural anaesthesia (risk of spinal haematoma).

Heparin can suppress adrenal secretion of aldosterone leading to hyperkalemia, particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium, or taking potassium sparing drugs. The risk of hyperkalemia appears to increase with duration of therapy but is usually reversible. Plasma potassium should be measured in patients at risk before starting heparin therapy and in all patients treated for more than 7 days.

Heparin resistance

There is considerable variation in individual anticoagulant responses to heparin.

Heparin resistance, defined as an inadequate response to heparin at a standard dose for achieving a therapeutic goal occurs in approximately 5 to 30% of patients.

Factors predisposing to the development of heparin resistance, include:

• Antithrombin III activity less than 60% of normal (antithrombin III-dependent heparin resistance): Reduced antithrombin III activity may be hereditary or more commonly, acquired (secondary to preoperative heparin therapy in the main, chronic liver disease, nephrotic syndrome, cardiopulmonary bypass, low grade disseminated intravascular coagulation or drug induced, e.g. by aprotinin, oestrogen or possibly nitroglycerin)

• Patients with normal or supranormal antithrombin III levels (antithrombin III-independent heparin resistance)
	• Thromboembolic disorders
	• Increased heparin clearance

• Elevated levels of heparin binding proteins, factor VIII, von Willebrand factor, fibrinogen, platelet factor 4 or histidine-rich glycoprotein
	• Active infection (sepsis or endocarditis) • Preoperative intra-aortic balloon counterpulsation • Thrombocytopenia • Thrombocytosis • Advanced age • Plasma albumin concentration • Relative hypovolaemia

Heparin resistance is also often encountered in acutely ill patients, in patients with malignancy and during pregnancy or the post-partum period.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Analgesics: Drugs that interfere with platelet aggregation eg. aspirin and other NSAIDs should be used with care. Increased risk of haemorrhage with ketorolac (avoid concomitant use even with low-dose heparin).

Anticoagulants, platelet inhibitors, etc: Increased risk of bleeding with oral anticoagulants, epoprostenol, clopidogrel, ticlopidine, streptokinase, dipyridamole, dextran solutions, or any other drug which may interfere with coagulation.

Cephalosporins: Some cephalosporins, e.g. cefaclor, cefixime and ceftriaxone, can affect the coagulation process and may therefore increase the risk of haemorrhage when used concurrently with heparin.

ACE inhibitors: Hyperkalaemia may occur with concomitant use.

Nitrates: Reduced activity of heparin has been reported with simultaneous intravenous glyceryl trinitrate infusion.

Probenecid: May increase the anticoagulant effects of heparin.

Tobacco smoke: Nicotine may partially counteract the anticoagulant effect of heparin. Increased heparin dosage may be required in smokers.

Interference with diagnostic tests may be associated with pseudo-hypocalcaemia (in haemodialysis patients), artefactual increases in total thyroxine and triiodothyronine, simulated metabolic acidosis and inhibition of the chromogenic lysate assay for endotoxin. Heparin may interfere with the determination of aminoglycosides by immunoassays.

4.6 Pregnancy And Lactation

Heparin is not contraindicated in pregnancy. Heparin does not cross the placenta or appear in breast milk. The decision to use heparin in pregnancy should be taken after evaluation of the risk/benefit in any particular circumstances.

Reduced bone density has been reported with prolonged heparin treatment during pregnancy.

Haemorrhage may be a problem during pregnancy or after delivery.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

Haemorrhage (see also Special Warnings and Precautions and Overdosage Information).

Adrenal insufficiency secondary to adrenal haemorrhage has been associated with heparin (rarely).

Thrombocytopenia has been observed occasionally (see also Special Precautions and Warnings). Two types of heparin-induced thrombocytopenia have been defined. Type I is frequent, mild (usually>50 x 10⁹/L) and transient, occurring within 1-5 days of heparin administration. Type II is less frequent but often associated with severe thrombocytopenia (usually <50 x 10⁹/L). It is immune-mediated and occurs after a week or more (earlier in patients previously exposed to heparin). It is associated with the production of a platelet-aggregating antibody and thromboembolic complications which may precede the onset of thrombocytopenia. Heparin should be discontinued immediately.

There is some evidence that prolonged dosing with heparin (ie. over many months) may cause alopecia and osteoporosis. Significant bone demineralisation has been reported in women taking more than 10,000 I.U. per day of heparin for at least 6 months.

Heparin products can cause hypoaldosteronism which may result in an increase in plasma potassium. Rarely, clinically significant hyperkalemia may occur particularly in patients with chronic renal failure and diabetes mellitus (see Warnings and Precautions).

Hypersensitivity reactions to heparin are rare. They include urticaria, conjunctivitis, rhinitis, asthma, cyanosis, tachypnoea, feeling of oppression, fever, chills, angioneurotic oedema and anaphylactic shock.

Local irritation and skin necrosis may occur but are rare.

Priapism has been reported. Increased serum transaminase values may occur but usually resolve on discontinuation of heparin. Heparin administration is associated with release of lipoprotein lipase into the plasma; rebound hyperlipidaemia may follow heparin withdrawal.

4.9 Overdose

A potential hazard of heparin therapy is haemorrhage, but this is usually due to overdosage and the risk is minimised by strict laboratory control. Slight haemorrhage can usually be treated by withdrawing the drug. If bleeding is more severe, clotting time and platelet count should be determined. Prolonged clotting time will indicate the presence of an excessive anticoagulant effect requiring neutralisation by intravenous protamine sulphate, at a dosage of 1 mg for every 100 I.U. of heparin to be neutralised. The bolus dose of protamine sulphate should be given slowly over about 10 minutes and not exceed 50 mg. If more than 15 minutes have elapsed since the injection of heparin, lower doses of protamine will be necessary.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Heparin is an anticoagulant and acts by inhibiting thrombin and by potentiating the naturally occurring inhibitors of activated Factor X (Xa).

5.2 Pharmacokinetic Properties

As heparin is not absorbed from the gastrointestinal tract and sublingual sites it is administered by injection. After injection heparin extensively binds to plasma proteins.

Heparin is metabolised in the liver and the inactive metabolic products are excreted in the urine.

The half life of heparin is dependent on the dose.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to those already included in other sections.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Water for injections

Sodium hydroxide solution 3M

Hydrochloric acid 3M

6.2 Incompatibilities

Heparin is incompatible with many injectable preparations e.g. some antibiotics, opioid analgesics and antihistamines.

The following drugs are incompatible with heparin;

Alteplase, amikacin sulphate, amiodarone hydrochloride, ampicillin sodium, aprotinin, benzylpenicillin potassium or sodium, cefalotin sodium, chlorpromazine hydrochloride, ciprofloxacin lactate, cisatracurium besilate, cytarabine, dacarbazine, daunorubicin hydrochloride, diazepam, doxorubicin hydrochloride, droperidol, erythromycin lactobionate, gentamicin sulphate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, kanamycin sulphate, labetolol hydrochloride, meticillin sodium, methotrimeprazine, netilmicin sulphate, nicardipine hydrochloride, oxytetracycline hydrochloride, pethidine hydrochloride, polymyxin B sulphate, promethazine hydrochloride, streptomycin sulphate, tobramycin sulphate, triflupromazine hydrochloride, vancomycin hydrochloride and vinblastine sulphate.

Dobutamine hydrochloride and heparin should not be mixed or infused through the same intravenous line, as this causes precipitation.

Heparin and reteplase are incompatible when combined in solution.

If reteplase and heparin are to be given through the same line this, together with any Y-lines, must be thoroughly flushed with a 0.9% saline or a 5% glucose solution prior to and following the reteplase injection.

6.3 Shelf Life

Unopened - 36 months

From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately.

If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special Precautions For Storage

Do not store above 25^oC

Store in the original package

6.5 Nature And Contents Of Container

Neutral glass ampoules (Type I Ph Eur) of 1ml or 2ml, 5ml, 10ml and 20ml capacity containing 1ml, 5ml, 10ml and 20ml of solution respectively. Cartons contain 10 ampoules.

6.6 Special Precautions For Disposal And Other Handling

Not applicable

7. Marketing Authorisation Holder

Wockhardt UK Ltd

Ash Road North

Wrexham

LL13 9UF

UK.

8. Marketing Authorisation Number(S)

PL 29831/0105

MA 154/02001

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 7 September 2007 (UK)

10. Date Of Revision Of The Text

18/09/2009.