Fluvermox

Fluvermox may be available in the countries listed below.

Ingredient matches for Fluvermox

Flubendazole

Flubendazole is reported as an ingredient of Fluvermox in the following countries:

• Venezuela

International Drug Name Search

Pentetate zinc trisodium

1000 mg

For Intravenous or Inhalation Administration

Package Insert - Instruction for Use

Pentetate zinc trisodium Description

Pentetate zinc trisodium injection contains the sodium salt of zinc diethylenetriaminepentaacetate. Pentetate zinc trisodium is also known as trisodium zinc diethylenetriaminepentaacetate and is commonly referred to as Zn-DTPA. It has a molecular formula of Na3ZnC14H18N3O10 and a molecular weight of 522.7 Daltons. It is represented by the following structural formula:

Zn-DTPA is supplied as a clear, colorless, hyperosmolar (1260 mOsmol/kg) solution in a colorless ampoule containing 5 mL. The ampoule contents are sterile, non-pyrogenic and suitable for intravenous administration. Each mL of solution contains the equivalent of 200 mg Pentetate zinc trisodium (obtained from 150.51 mg pentetic acid, 31.14 mg zinc oxide and NaOH) and water for injection, USP. The pH of the solution is adjusted with NaOH and is between 6.5 – 7.5.

Pentetate zinc trisodium - Clinical Pharmacology

General

Zn-DTPA forms stable chelates with metal ions by exchanging zinc for a metal of greater binding capacity. The radioactive chelates are then excreted by glomerular filtration into the urine. In animal studies, Zn-DTPA forms less stable chelates with uranium and neptunium in vivo resulting in deposition of these elements in tissues including the bone. Zn-DTPA treatments are not expected to be effective for uranium and neptunium. Radioactive iodine is not bound by DTPA.

Pharmacodynamics

In a study of rodents internally contaminated with plutonium, the rate of plutonium elimination was measured after treatment with Ca-DTPA and Zn-DTPA given intravenously as a single dose of 10 to 1,000 µmol/kg (0.54 – 54 × maximum human dose, MHD). When treated within one hour of internal contamination, Ca-DTPA resulted in about a 10-fold higher rate of elimination of plutonium in the urine as compared to Zn-DTPA. The chelating capacity of Ca-DTPA is greatest immediately and up to approximately 24 hours after internal contamination when the radiocontaminant is still circulating and readily available for chelation. After the first dose of Ca-DTPA, maintenance treatment with either Ca-DTPA or Zn-DTPA resulted in similar rates of elimination of radioactivity. However, at comparable doses, Zn-DTPA had less toxicity (e.g., less depletion of trace metals, lower rate of mortality, the absence of kidney and liver vacuolization, and absence of small bowel hemorrhagic lesions).

In another study, rodents contaminated with aerosolized plutonium and americium were treated with Ca-DTPA and Zn-DTPA. The treatment schedule involved inhalation of Ca-DTPA 2 µmol/kg (0.11 MHD) 30 minutes after contamination followed by inhalation of Zn-DTPA 2 µmol/kg at approximately 6 hours, 1, 2, 3, and 6 days, then twice weekly to day 26 or day 27. The treatment regime reduced the lung deposit of plutonium and americium to 1-2% of that in untreated animals. Systemic deposit in liver and skeleton were reduced by half.

Literature and U.S. Registry data in humans indicate that intravenous administration of Zn-DTPA forms chelates with radioactive contaminants found in the circulation, interstitial fluid, and tissues. When Zn-DTPA is administered by inhalation, it can chelate transuranium elements. Expectoration is expected to decrease the amount of radioactive contaminant available for systemic absorption.

The effectiveness of chelation decreases with time after internal contamination because the transuranium elements become incorporated into the tissues. Chelation treatment should be given as soon as possible after known or suspected internal contamination with transuranium elements has occurred. (See DOSAGE ADMINISTRATION)

Pharmacokinetics

Plasma retention and urinary excretion data were obtained in 2 subjects that received 750 kBq of 14C-DTPA. As shown in Figure 1, the radiolabeled DTPA was rapidly distributed throughout the extracellular fluid space and was cleared by glomerular filtration. The plasma retention up to 7 hours post dosing was expressed by the sum of three exponential components with average half-lives of 1.4 min, 14.5 min, and 94.4 min. The level of activity in the plasma was below the limit of detection 24 hours after injection. During the study, no detectable activity was exhaled or excreted in the feces. By 24 hours, cumulative urinary excretion was more than 99% of the injected dose.

Absorption

Zn-DTPA is poorly absorbed in the GI tract. In animal studies, after oral administration, absorption was approximately 5%. In a U.S. Registry of 18 patients who received a single inhaled or intravenous dose of 1 gram, urine data indicate that the inhaled product was absorbed and resulted in a comparable elimination of the radiocontaminant. One study of 2 human subjects that received Ca-DTPA with 14C-DTPA by inhalation revealed approximately 20% absorption from the lungs. Human or animal bioavailability comparisons for Zn-DTPA are not available after administration by inhalation and intravenous injection. (See CLINICAL PHARMACOLOGY, Clinical Trials)

Distribution

Following intravenous administration, Zn-DTPA is rapidly distributed throughout the extracellular fluid space. No significant amount of Zn-DTPA penetrates into erythrocytes or other cells. No accumulation of Zn-DTPA in specific organs has been observed. There is little or no binding of the chelating agent by the renal parenchyma.

Metabolism

Zn-DTPA undergoes a minimal amount of metabolic change in the body.

Adverse Metabolic Effects

Zn-DTPA results in minimal depletion of magnesium and manganese.

Elimination

Zn-DTPA is cleared from the plasma in the first few hours after dosing through urinary excretion by glomerular filtration. Renal tubular excretion has not been documented. In stool samples, only a very small amount of radioactivity (<3%) was detected.

Renal Impaired and/or Compromised Liver Function Patients

Adequate and well-controlled pharmacokinetic and pharmacodynamic studies in renally impaired and/or hepatically impaired patients were not identified in the literature. Both Zn-DTPA and its radioactive chelates are excreted by glomerular filtration. Impaired renal function may decrease their rates of elimination and increase the serum half-life of Zn-DTPA.

Clinical trials

All clinical data has come from the treatment of individuals who were accidentally contaminated. Observational data were maintained in a U.S. Registry of individuals with internal radiation contamination primarily from acute occupational contamination with plutonium, americium and curium.

In 286 individuals, bioassays were available to measure urinary radioactivity elimination after chelation therapy. Of these 286 individuals, only 18 had matched pre- and post-chelator urine radioactivity bioassay results available. The majority of these individuals received Ca-DTPA as the initial component to their chelation therapy. When multiple chelator doses were administered over days, the standard of practice was to switch therapy to Zn-DTPA following an initial dose of Ca-DTPA. Although both chelators were considered equipotent 24 hours following internal contamination, Zn-DTPA was considered less toxic. In one individual who received 3 doses, 1 gram each, by nebulization (1:1 Zn-DTPA and saline) followed by 6 intravenous doses, the urinary excretion of plutonium after the first nebulized dose was increased by a factor of 45.

After initial treatment with Ca-DTPA, maintenance treatment was continued with daily 1 gram Zn-DTPA doses administered over a period of days, months or years, depending on the extent of internal contamination and individual response to therapy. Treatment was generally continued until the excretion enhancement factor (EEF) approached 1. The longest treatment duration was 3.5 years. Similar increases in urinary radioactivity elimination were supported by data from the remaining 268 individuals in the U.S. Registry and from the literature.

Indications and Usage for Pentetate zinc trisodium

Zn-DTPA is indicated for treatment of individuals with known or suspected internal contamination with plutonium, americium, or curium to increase the rates of elimination.

Contraindications

None known.

Warnings

Nebulized chelation therapy may be associated with exacerbation of asthma. Caution should be exercised when administering Zn-DTPA by the inhalation route. (See ADVERSE REACTIONS)

Precautions

General

Treatment over several months with Zn-DTPA could lead to depletion of body stores of endogenous metals (e.g., magnesium, manganese). These elements should be monitored routinely and, if appropriate, mineral or vitamin plus mineral supplements should be provided.

Information for Patients

Radioactive metals are known to be excreted in the urine, feces, and breast milk. In individuals with recent internal contamination with plutonium, americium, or curium, Zn-DTPA treatment increases excretion of radioactivity in the urine. Appropriate safety measures should be taken to minimize contamination of others. When possible, a toilet should be used instead of a urinal, and it should be flushed several times after each use. Spilled urine or feces should be cleaned up completely and patients should wash their hands thoroughly. If blood or urine comes in contact with clothing or linens, they should be washed separately. Patients should drink plenty of fluids and void frequently. If patients are coughing, any expectorant should be disposed of carefully. Swallowing the expectorant should be avoided if possible. Parents and child-care givers should take extra precaution in handling the urine, feces, and expectorants of children to avoid any additional exposure to either the caregiver or to the child. Nursing mothers should take extra precaution in disposing of breast milk. (See PRECAUTIONS, Nursing Mothers)

Laboratory Tests

Serum electrolytes and essential metals should be closely monitored during Zn-DTPA treatment. Mineral or vitamin plus mineral supplements may be given as appropriate. (See PRECAUTIONS)

Drug-Drug Interactions

Adequate and well-controlled drug-drug interaction studies in humans were not identified in the literature. When an individual is contaminated with multiple radiocontaminants, or when the radiocontaminants are unknown, additional therapies may be needed (e.g., Prussian blue, potassium iodide).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Zn-DTPA to evaluate carcinogenesis, mutagenesis and impairment of fertility have not been performed. Data for Zn-DTPA effects on spermatogenesis are not available.

Teratogenic Effects

Pregnancy Category B

There are no human pregnancy outcome data from which to assess the risk of Zn-DTPA exposure on fetal development. Reproduction studies have been performed in pregnant mice at doses up to 11.5 mmol/kg (31 times the recommended daily dose of 1 gram based on body surface area [BSA] adjusted dose) and have revealed no evidence of impaired fertility or harm to the fetus. There was a slight reduction in the average birth weight.

Treatment of pregnant women should begin and continue with Zn-DTPA. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. The risk of toxicity from untreated internal radioactive contamination should be weighed against the risk of Zn-DTPA treatment.

Nursing Mothers

Studies to determine if Zn-DTPA is excreted in breast milk have not been conducted.

Radiocontaminants are known to be excreted in breast milk. Women with known or suspected internal contamination with radiocontaminants should not breast feed, whether or not they are receiving chelation therapy. Precautions should be taken when discarding breast milk. (See PRECAUTIONS, Information for Patients)

Pediatric Use

The safety and effectiveness of Zn-DTPA was established in the adult population and efficacy was extrapolated to the pediatric population for the intravenous route based on the comparability of pathophysiologic mechanisms. The dose is based on body size adjustment for an intravenous drug that is renally cleared. The safety and effectiveness of the nebulized route of administration has not been established in the pediatric population.

Adverse Reactions

In the U.S. Registry, a total of 646 individuals received at least one dose of either Ca-DTPA or Zn-DTPA. Of these, 62 received Zn-DTPA by one or more routes of administration. Forty-eight individuals were dosed by intravenous administration, 18 by inhalation and 8 by other or unknown routes of administration.

Of the individuals that received Zn-DTPA, 23/62 (37%) received one dose and 8 (13%) received two doses. The remaining 31 individuals received three or more doses. The largest number of Zn-DTPA doses to a single individual was 574 doses delivered over 3.5 years.

Overall, the presence or absence of adverse events was recorded in 310/646 individuals. Of these 19 (6.1%) individuals reported at least one adverse event. The total number of recorded adverse events was 20. Of the 20 adverse events, 1 individual treated with Zn-DTPA reported headache, lightheadedness, and pelvic pain.

Two individuals experienced cough and/or wheezing with nebulized Ca-DTPA therapy however there was no report of such events with nebulized Zn-DTPA.

Overdosage

Overdose with Zn-DTPA has not been reported.

Pentetate zinc trisodium Dosage and Administration

Chelation treatment is most effective if administered within the first 24 hours after internal contamination and should be started as soon as possible after suspected or known internal contamination. However, even when treatment cannot be started right away, individuals should be given chelation treatment as soon as it becomes available. Chelation treatment is still effective even after time has elapsed following internal contamination, however the chelating effects of Zn-DTPA are greatest when the radiocontaminants are still circulating or are in interstitial fluids. The effectiveness of chelation decreases with time following internal contamination as the radiocontaminants become sequestered in liver and bone.

Individuals should drink plenty of fluids and void frequently to promote dilution of the radioactive chelate in the urine and minimize radiation exposure directly to the bladder.

If internal contamination with radiocontaminants other than plutonium, americium, or curium, or unknown radiocontaminants is suspected, additional therapies may be needed (e.g., Prussian blue, potassium iodide).

Initial Dose

IT IS PREFERABLE TO ADMINISTER CA-DTPA, IF AVAILABLE, AS THE INITIAL DOSE DURING THE FIRST 24 HOURS AFTER INTERNAL CONTAMINATION BECAUSE CA-DTPA IS MORE EFFECTIVE THAN ZN-DTPA DURING THIS TIME PERIOD. AFTER 24 HOURS, ZN-DTPA AND CA-DTPA ARE EQUALLY EFFECTIVE.

Adults and Adolescents

A single 1.0 gram initial dose of Zn-DTPA administered intravenously.

Pediatrics (less than 12 years of age)

A single initial dose of 14 mg/kg administered intravenously not to exceed 1.0 gram.

Renally impaired patients

No dose adjustment is needed. However, renal impairment may reduce the rate at which chelators remove radiocontaminants from the body. In heavily contaminated patients with renal impairment, dialysis may be used to increase the rate of elimination. High efficiency high flux dialysis is recommended. Because dialysis fluid will become radioactive, radiation precautions must be taken to protect personnel, other patients, and the general public.

Maintenance Treatment

Adults and Adolescents

The recommended maintenance dose of Zn-DTPA is 1.0 gram once a day administered intravenously.

Pediatrics (less than 12 years of age)

The recommended maintenance dose of Zn-DTPA is 14 mg/kg once a day administered intravenously. The maximum daily dose should not exceed 1.0 gram per day.

Renally impaired patients

No dose adjustment is needed.

The duration of chelation treatment depends on the amount of internal contamination and individual response to treatment. (See Monitoring)

Methods of Administration

The intravenous route is recommended and should be used if the route of internal contamination is not known or if multiple routes of internal contamination are likely. Zn-DTPA solution (1 gram in 5 mL) should be administered either with a slow intravenous push over a period of 3-4 minutes or by intravenous infusion over 30 minutes diluted in 100-250 mL of 5% dextrose in water (D5W), Ringers Lactate, or Normal Saline.

In individuals whose internal contamination is only by inhalation, Zn-DTPA can be administered by nebulized inhalation as an alternative route of administration. Zn-DTPA should be diluted for nebulization at a 1:1 ratio with sterile water or saline. After nebulization, individuals should be encouraged to avoid swallowing any expectorant. Some individuals may experience respiratory adverse events after inhalation therapy. (See WARNINGS) The safety and effectiveness of the nebulized route of administration has not been established in the pediatric population.

The safety and effectiveness of the intramuscular route of injection have not been established.

Handling

OPC ampoule: to open, turn so that the point faces upward and break off the neck with a downward movement.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The product may be filtered using a sterile filter if particles are seen subsequent to opening of the ampoule.

Monitoring

When possible, obtain baseline blood and urine samples (CBC with differential, BUN, serum chemistries and electrolytes, urinalysis and blood and urine radioassays) before initiating treatment.

To establish an elimination curve, a quantitative baseline estimate of the total internalized transuranium element(s) and measures of elimination of radioactivity should be obtained by appropriate whole-body counting, by bioassay (e.g., biodosimetry), or fecal/urine sample whenever possible.

During Treatment

• Measure the radioactivity in blood, urine, and fecal samples weekly to monitor the radioactive contaminant elimination rate.


• Monitor CBC with differential, BUN, serum chemistries and electrolytes, and urinalysis measurements regularly.


• Record any adverse events from Zn-DTPA.

How is Pentetate zinc trisodium Supplied

Zn-DTPA is supplied as a sterile solution in 5 mL single-use clear glass ampoules at a concentration of 200 mg/mL for intravenous use. Each ampoule contains the equivalent of 1000 mg of Pentetate zinc trisodium.

NDC 52919-002-03, 5 mL single-use ampoules, package of 10.

Storage

Store between 15 - 30°C (59 - 86°F).

COLLECTION OF PATIENT TREATMENT DATA

To develop long-term response data and information on the risk of developing late malignancy, detailed information on patient treatment should be provided to the manufacturer (see Patient Treatment Data Form. In the case you need additional forms, please use the enclosed form as a template or see the following website: www.zn-dtpa.com). These data should include a record of the radioactive body burden and bioassay results at defined time intervals, a description of measurement methods to facilitate analysis of data, and adverse events.

Questions regarding the use of Zn-DTPA for the treatment of internal contamination with transuranium elements may be referred to:

hameln pharmaceuticals gmbh

Langes Feld 13

31789 Hameln, Germany

Tel.: +49-5151-581-0

Fax.: +49-5151-581-258

e-mail: welcome@hm-ph.com

contact person: Dr. Mathias Dewald

Tel.: +49-5151-581-214

Fax.: +49-5151-581-581

e-mail: m.dewald@hm-ph.com

hameln

pharmaceuticals

44640/19/05

Pentetate zinc trisodium  Pentetate zinc trisodium  injection, solution, concentrate

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 52919-002 Route of Administration INTRAVENOUS, RESPIRATORY (INHALATION) DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Pentetate zinc trisodium (pentetic acid) Active 200 MILLIGRAM  In 1 MILLILITER water Inactive   zinc oxide Inactive   sodium hydroxide Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 52919-002-03 10 AMPULE In 1 PACKAGE contains a AMPULE 1 5 mL (MILLILITER) In 1 AMPULE This package is contained within the PACKAGE (52919-002-03)

Revised: 12/2006Hameln Pharmaceuticals

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• Pentetate zinc trisodium Use in Pregnancy & Breastfeeding
• Pentetate zinc trisodium Support Group
• 0 Reviews for Pentetate zinc trisodium - Add your own review/rating

• pentetate zinc trisodium Intravenous, Inhalation, oral/nebulization Advanced Consumer (Micromedex) - Includes Dosage Information

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• Radiation Emergency

Indomin

Indomin may be available in the countries listed below.

Ingredient matches for Indomin

Indometacin

Indometacin is reported as an ingredient of Indomin in the following countries:

• Bahrain


• Egypt


• Iraq


• Jordan


• Kuwait


• Lebanon


• Libya


• Oman


• Qatar


• Saudi Arabia


• Sudan


• Syria


• United Arab Emirates


• Yemen

International Drug Name Search

Pyrethrins/Piperonyl Gel

Pronunciation: pye-REE-thrins/pye-PEER-i-nil
Generic Name: Pyrethrins/Piperonyl
Brand Name: Examples include RID and Lice Treatment

Pyrethrins/Piperonyl Gel is used for:

Treating head, pubic (crab), or body lice.

Pyrethrins/Piperonyl Gel is a pediculicide combination. It works by interfering with the nerves of the lice, which causes death of the lice.

Do NOT use Pyrethrins/Piperonyl Gel if:

• you are allergic to any ingredient in Pyrethrins/Piperonyl Gel

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

Before using Pyrethrins/Piperonyl Gel:

Some medical conditions may interact with Pyrethrins/Piperonyl Gel. 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, including ragweed


• if you have skin irritation

Some MEDICINES MAY INTERACT with Pyrethrins/Piperonyl Gel. Because little, if any, of Pyrethrins/Piperonyl Gel is absorbed into the blood, the risk of it interacting with another medicine is low.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Pyrethrins/Piperonyl Gel 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 Pyrethrins/Piperonyl Gel:

Use Pyrethrins/Piperonyl Gel as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Pyrethrins/Piperonyl Gel is for external use only. Pyrethrins/Piperonyl Gel is not to be used for lice in the eyebrows or eyelashes. Contact a doctor if lice are present in these areas.


• Use Pyrethrins/Piperonyl Gel on dry hair.


• Apply to the affected area until all hair is completely wet. Allow Pyrethrins/Piperonyl Gel to remain on the affected area for no more than 10 minutes. Add sufficient warm water to form a lather and shampoo as usual. Rinse completely. Close eyes tightly and protect them with a washcloth or towel when rinsing Pyrethrins/Piperonyl Gel out of the hair.


• Use a fine-toothed comb to remove dead lice or eggs (nits) from hair.


• Check daily for any lice or eggs that you missed.


• Repeat this treatment in 7 to 10 days to kill any newly hatched lice.


• If infestation continues, contact a doctor for other treatments.


• If you miss a dose of Pyrethrins/Piperonyl Gel, use it as soon as you remember. Continue to use it as directed by your doctor.

Ask your health care provider any questions you may have about how to use Pyrethrins/Piperonyl Gel.

Important safety information:

• Do not get Pyrethrins/Piperonyl Gel in your eyes, vagina, nose, or mouth. If you get Pyrethrins/Piperonyl Gel in your eyes, flush them with cool tap water.


• Do not inhale Pyrethrins/Piperonyl Gel. Use Pyrethrins/Piperonyl Gel in a well-ventilated area.


• All hats, scarves, coats, clothes, underwear, and bed linens should be dry cleaned or washed in hot water and dried on the hot cycle of the dryer for at least 20 minutes. Hair combs and brushes should also be cleaned in hot water.


• All members of the household should be examined for the presence of lice and treated if lice are found.


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

Possible side effects of Pyrethrins/Piperonyl Gel:

All medicines may cause side effects, but many people have no, or minor, side effects. No COMMON side effects have been reported with the proper use of Pyrethrins/Piperonyl Gel. 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); eye irritation; infection; persistent skin or scalp irritation; skin tenderness.

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.

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. Symptoms may include coughing; diarrhea; difficulty breathing; headache; nausea; unusual dizziness or drowsiness; vomiting.

Proper storage of Pyrethrins/Piperonyl Gel:

Store Pyrethrins/Piperonyl Gel 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 Pyrethrins/Piperonyl Gel out of the reach of children and away from pets.

General information:

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


• Pyrethrins/Piperonyl Gel 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 Pyrethrins/Piperonyl Gel. 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.

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• Head Lice
• Lice

Prezista

Generic Name: Darunavir
Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: [(1S,2R) - 3 - [[(4 - Aminophenyl)sulfonyl](2 - methylpropyl)amino] - 2 - hydroxy - 1 - (phenylmethyl)propyl] - carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester
Molecular Formula: C₂₇H₃₇N₃O₇SC₂₇H₃₇N₃O₇S•C₂H₅OH
CAS Number: 206361-99-1

Introduction

Antiretroviral; HIV protease inhibitor (PI).^{1 2 3}

Uses for Prezista

Treatment of HIV Infection

Treatment of HIV infection.¹ Used in conjunction with low-dose ritonavir (ritonavir-boosted darunavir) and other antiretroviral agents.¹

Ritonavir-boosted darunavir is a preferred PI for initial treatment regimens in adults.⁴

Treatment-experienced patients: Use of ritonavir-boosted darunavir should be guided by genotypic and phenotypic viral resistance testing and the individual’s prior antiretroviral treatment.¹

Prezista Dosage and Administration

Administration

Oral Administration

Administer orally in conjunction with low-dose ritonavir (ritonavir-boosted darunavir).^{1 4} Do not use without low-dose ritonavir.¹

Take darunavir and low-dose ritonavir at same time and with food.¹

Administered once daily in treatment-naive adults.¹

Administered twice daily in pediatric patients and treatment-experienced adults.¹

Ensure that pediatric patients can swallow tablets; those unable to swallow tablets are not candidates for ritonavir-boosted darunavir therapy.¹

Dosage

Available as darunavir ethanolate; dosage expressed in terms of darunavir.¹

Pediatric Patients

Treatment of HIV Infection

To avoid medication errors, use extra care in calculating the dose, transcribing the medication order, dispensing the prescription, and providing dosing instructions.¹

Dosage of ritonavir-boosted darunavir in children 6–<18 years of age weighing at least 20 kg is based on weight.¹

Table 1: Dosage for Ritonavir-boosted Darunavir for Pediatric Patients 6–<18 Years of Age1

Body weight	Darunavir dosage	Ritonavir dosage
20 to < 30 kg	375 mg twice daily	50 mg twice daily
30 to < 40 kg	450 mg twice daily	60 mg twice daily
≥ 40 kg	600 mg twice daily	100 mg twice daily

Adults

Treatment of HIV Infection

Treatment-naive Adults

Oral

800 mg once daily boosted with low-dose ritonavir (100 mg once daily).¹

Treatment-experienced Adults

Oral

600 mg twice daily boosted with low-dose ritonavir (100 mg twice daily).¹

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Do not exceed dosage for treatment-experienced adults.¹

Special Populations

Hepatic Impairment

Dosage adjustment not needed in patients with mild to moderate hepatic impairment (Child-Pugh class A or B).^{1 4} Do not use in those with severe hepatic impairment (Child-Pugh class C).^{1 4}

Renal Impairment

Some experts state that dosage adjustments are not necessary.⁴

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Cautions for Prezista

Contraindications

• 
  

  Concomitant use with drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events and other drugs that may lead to loss of virologic response (e.g., cisapride, ergot alkaloids, lovastatin, oral midazolam, pimozide, rifampin, simvastatin, St. John’s wort [Hypericum perforatum], triazolam).¹ (See Specific Drugs under Interactions.)

  
  

Warnings/Precautions

Warnings

Hepatic Effects

Acute hepatitis reported in clinical studies.¹ Liver injury (in some cases fatal) reported during postmarketing surveillance; liver injury generally occurred in patients with advanced HIV infection who were receiving multiple concomitant drugs, who were coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV), and/or were developing immune reconstitution syndrome.¹

Conduct appropriate laboratory tests before starting darunavir; monitor periodically thereafter.¹ Consider increased AST/ALT monitoring in patients with hepatitis, cirrhosis, or elevated transaminase values prior to therapy, especially during the first several months of therapy.¹

Consider interrupting or discontinuing darunavir in patients who develop manifestations suggestive of hepatic impairment (e.g., fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly, clinically important increases in hepatic enzyme concentrations).¹

Interactions

Darunavir is administered concomitantly with low-dose ritonavir (ritonavir-boosted darunavir).¹ Failure to administer with recommended low-dose ritonavir will result in subtherapeutic darunavir concentrations and inadequate antiviral response.¹ The usual cautions, precautions, and contraindications associated with ritonavir should be considered.¹

Concomitant use with certain drugs is not recommended or requires particular caution (e.g., sildenafil, tadalafil, vardenafil).^{1 4} (See Specific Drugs under Interactions.)

Hyperglycemic and Diabetogenic Effects

Hyperglycemia (potentially persistent), new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of PIs; diabetic ketoacidosis has occurred.¹

Initiate or adjust antidiabetic therapy (e.g., insulin, oral hypoglycemic agents) as needed.¹

Sensitivity Reactions

Sulfonamide Sensitivity

Darunavir contains a sulfonamide moiety; use with caution in patients with known sulfonamide allergy.¹

Dermatologic Reactions

Severe skin reactions, including Stevens-Johnson syndrome reported;¹ fever and increased serum transaminase concentrations also may occur.¹

Discontinue darunavir if severe rash occurs.¹

General Precautions

Hemophilia A and B

Spontaneous bleeding reported with PIs;¹ causal relationship not established.¹

Use with caution in patients with history of hemophilia A or B.¹ Increased hemostatic therapy (e.g., antihemophilic factor) may be needed.¹

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and general cushingoid appearance.¹

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]; this may necessitate further evaluation and treatment.¹

HIV Resistance

Possibility of cross-resistance to other PIs not evaluated.¹ Effect of ritonavir-boosted darunavir therapy on subsequent therapy with other PIs unknown.¹

Specific Populations

Pregnancy

Category C.¹

Antiretroviral Pregnancy Registry at 800-258-4263.¹

Some experts state safety and pharmacokinetic data insufficient to recommend ritonavir-boosted darunavir in pregnant women.⁷

Lactation

Distributed into milk in rats;¹ not known whether distributed into human milk.¹

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.¹

Pediatric Use

Adverse effects in children 6–<18 years of age similar to those reported in adults.¹

Safety, efficacy, and pharmacokinetic profile not established in children 3 to <6 years of age.¹

Should not be used in children <3 years of age because of toxicity and mortality in juvenile rats.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Use with caution and monitor because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Hepatic Impairment

Risk for liver function abnormalities, including severe adverse hepatic effects, in patients with preexisting hepatic impairment, including those with HBV or HCV infection.¹

Pharmacokinetics not altered in individuals with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.¹

Use not recommended in patients with severe hepatic impairment.¹

Renal Impairment

Pharmacokinetics not altered in patients with Cl_cr≥30 mL/minute.¹ Not studied in patients with severe renal impairment or end-stage renal disease.¹

Common Adverse Effects

Diarrhea,^{1 9} nausea,^{1 9} headache,^{1 9} abdominal pain.¹

Interactions for Prezista

Darunavir metabolized principally by CYP3A.¹

Darunavir and ritonavir inhibit CYP3A4 and CYP2D6.¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors or inducers of CYP3A4 with possible alteration in metabolism of darunavir or ritonavir.¹

Potential pharmacokinetic interaction with drugs metabolized by CYP3A or CYP2D6 with possible altered metabolism of drug metabolized by CYP3A or CYP2D6.¹

Specific Drugs

Drug	Interaction	Comments
Abacavir	Pharmacokinetic interaction not expected1 No in vitro evidence of antagonistic antiretroviral effects 1
Antiarrhythmic agents (amiodarone, flecainide, systemic lidocaine, propafenone, quinidine)	Possible increased plasma concentrations of antiarrhythmic agents1	Monitor antiarrhythmic concentrations1
Anticoagulants	Decreased warfarin concentrations1	Monitor INR 1
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Carbamazepine: Increased carbamazepine concentrations1 Phenobarbital, phenytoin: Decreased concentrations of the anticonvulsant1	Carbamazepine: Dosage adjustment not needed; monitor carbamazepine concentrations and adjust dose to achieve appropriate clinical effect1 Phenobarbital, phenytoin: Monitor anticonvulsant concentrations1
Antifungals (itraconazole, ketoconazole, voriconazole)	Itraconazole: Increased darunavir and itraconazole concentrations1 Ketoconazole: Increased darunavir and ketoconazole concentrations1 Voriconazole: Decreased voriconazole concentrations1	Itraconazole: Dosage >200 mg daily not recommended1 4 Ketoconazole: Dosage >200 mg daily not recommended 1 4 Voriconazole: Concomitant use not recommended unless benefits outweigh risks1 4
Antimycobacterials, rifamycins (rifabutin, rifampin, rifapentine)	Rifabutin: Increased rifabutin and darunavir concentrations1 Rifampin: Decreased darunavir concentrations; possible decreased antiretroviral activity1	Rifabutin: Reduce rifabutin dosage to 150 mg once every other day (further reduction may be needed); monitor for adverse effects1 4 Rifampin: Concomitant use contraindicated 1 4 Rifapentine: Concomitant use not recommended4
Atazanavir	Plasma concentration of atazanavir with ritonavir-boosted darunavir similar to ritonavir-boosted atazanavir; no change in darunavir concentrations1 No in vitro evidence of antagonistic antiretroviral effects1	Manufacturer and some experts state atazanavir 300 mg once daily can be used with ritonavir-boosted darunavir1 4
β-Adrenergic blocking agents (metoprolol, timolol)	Metoprolol, timolol: Possible increased concentrations of the β-adrenergic blocking agent1	Metoprolol, timolol: Caution; dose reduction of the β-adrenergic blocking agent may be needed1
Benzodiazepines (e.g., midazolam, triazolam)	Possible increased concentrations of midazolam or triazolam; potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression)1	Concomitant use with oral midazolam or triazolam contraindicated;1 some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation4
Calcium-channel blocking agents (e.g., felodipine, nicardipine, nifedipine)	Increased concentrations of calcium-channel blocking agents 1	Use concomitantly with caution; clinical monitoring recommended1
Cisapride	Potential for serious and/or life-threatening effects such as cardiac arrhythmias 1	Concomitant use contraindicated1
Clarithromycin	Increased clarithromycin concentrations1	Modification of usual clarithromycin dosage not necessary in patients with normal renal function; reduce clarithromycin dosage by 50% if Clcr 30–60 mL/minute and reduce by 75% if Clcr <30 mL/minute 1
Corticosteroids (dexamethasone, fluticasone)	Fluticasone nasal spray/oral inhalation: Increased fluticasone concentrations with ritonavir-boosted darunavir resulting in decreased cortisol concentrations1 4 Dexamethasone: Decreased darunavir concentration; possible decreased antiretroviral efficacy1	Fluticasone nasal spray/oral inhalation: Consider alternatives to fluticasone, especially when long-term corticosteroid use anticipated1 4
Delavirdine	No in vitro evidence of antagonistic antiretroviral effects 1
Didanosine	Didanosine delayed-release capsules: No change in didanosine or darunavir concentrations1 Conflicting administration instructions with didanosine and food1 No in vitro evidence of antagonistic antiretroviral effects 1	Administer darunavir with low-dose ritonavir (with food) 1 hour after or 2 hours before didanosine (without food)1
Digoxin	Increased digoxin concentrations1	Use lowest possible initial dose of digoxin; monitor digoxin concentrations and adjust dose as clinically indicated1
Dextromethorphan	Increased dextromethorphan concentrations1
Efavirenz	Decreased darunavir AUC; increased efavirenz AUC1 4 No in vitro evidence of antagonistic antiretroviral effects 1	Clinical importance unknown4 Some experts suggest usual dosages can be used with close monitoring; consider monitoring plasma darunavir and efavirenz concentrations4
Emtricitabine	Pharmacokinetic interaction not expected1 No in vitro evidence of antagonistic antiretroviral effects 1
Etravirine	Decrease in AUC of etravirine; no change in darunavir concentrations; safety and efficacy of ritonavir-boosted darunavir and etravirine established in clinical studies1 4	Dosage adjustment not needed1 4
Enfuvirtide	No in vitro evidence of antagonistic antiretroviral effects1
Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)	Potential for serious or life-threatening adverse effects (e.g., peripheral vasospasm, ischemia of extremities)1	Concomitant use contraindicated 1 If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving darunavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible7
Fosamprenavir	Data not available regarding pharmacokinetic interaction1	Concomitant use not recommended pending further data1
Histamine H2- receptor antagonists (e.g., ranitidine)	Ranitidine: Pharmacokinetic interaction not expected1 4	Dosage adjustment not necessary1
HMG-CoA reductase inhibitors	Lovastatin, simvastatin: Increased risk of serious adverse reactions (e.g., myopathy, rhabdomyolysis)1 Increased concentrations of certain HMG-CoA reductase inhibitors (i.e., atorvastatin, pravastatin, rosuvastatin)1 4	Concomitant use with lovastatin or simvastatin contraindicated1 If used with atorvastatin, pravastatin, or rosuvastatin, use lowest possible dosage of the HMG-CoA reductase inhibitor and monitor carefully; consider using fluvastatin1
Hormonal contraceptives (estrogens or progestins)	Decreased ethinyl estradiol and norethindrone concentrations with oral contraceptive preparations1	Use alternative nonhormonal contraception methods1
Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)	Potential for increased immunosuppressive agent concentrations1	Monitor plasma concentrations of immunosuppressive agent if used concomitantly1
Indinavir	Increased darunavir and indinavir concentrations1 No in vitro evidence of antagonistic antiretroviral effects1	Appropriate dosages for concomitant use not established1
Lamivudine	Pharmacokinetic interaction unlikely1 No in vitro evidence of antagonistic antiretroviral effects1
Lopinavir	No change in lopinavir concentrations; decreased darunavir concentrations1 No in vitro evidence of antagonistic antiretroviral effects1	Concomitant use not recommended1 4
Maraviroc	Increased maraviroc concentrations4	Recommended dosage of maraviroc is 150 mg twice daily when used with ritonavir-boosted darunavir4
Methadone	Decreased methadone concentrations1	Adjustment in the methadone dosage not needed; closely monitor for signs of opiate withdrawal and adjust methadone dosage if needed1
Nelfinavir	Data not available regarding pharmacokinetic interaction1 No in vitro evidence of antagonistic antiretroviral effects1	Concomitant use not recommended pending further data1
Nevirapine	Increased plasma nevirapine concentrations; unchanged plasma darunavir concentrations1 4 No in vitro evidence of antagonistic antiretroviral effects1	Dosage adjustment not necessary1 4
Proton pump inhibitors	Omeprazole: Decreased omeprazole concentrations1	Dosage adjustment not necessary1
Psychotherapeutic agents (e.g., desipramine, pimozide, risperidone, thioridazine, trazodone, SSRIs)	Pimozide: Potential for serious and/or life-threatening adverse effects (e.g., cardiac arrhythmias)1 Desipramine, trazodone: Potential for increased concentrations of the antidepressant; 1 increased risk of nausea, dizziness, hypotension, syncope1 SSRIs: Decreased concentrations of paroxetine and sertraline; unchanged darunavir concentrations1 4 Risperidone, thioridazine: Potential for increased concentrations of the psychotherapeutic agent1	Pimozide: Concomitant use contraindicated1 Desipramine, trazodone: Caution; reduced dosage of the antidepressant may be needed1 SSRIs: Titrate dosage of paroxetine or sertraline and monitor for clinical response1 4 Risperidone, thioridazine: Reduced dosage of the psychotherapeutic agent may be needed1
Ritonavir	Increased plasma darunavir concentrations and AUC;1 2 4 concomitant low-dose ritonavir used to therapeutic advantage (ritonavir-boosted darunavir)1 2 4 No in vitro evidence of antagonistic antiretroviral effects1
St. John’s wort (Hypericum perforatum)	Potential decreased darunavir concentration; possible decreased antiretroviral efficacy1	Concomitant use contraindicated1
Saquinavir	Decreased darunavir concentrations; unchanged saquinavir concentrations1 No in vitro evidence of antagonistic antiretroviral effects1	Concomitant use not recommended1 4
Sildenafil	Possible increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1	Do not exceed sildenafil dosage of 25 mg once every 48 hours; closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1 4
Stavudine	Pharmacokinetic interaction unlikely1 No in vitro evidence of antagonistic antiretroviral effects1
Tadalafil	Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1	Use with caution and with reduced tadalafil dosage (initial dosage of 5 mg and do not exceed a single dose of 10 mg in 72 hours);4 closely monitor for adverse effects1 4
Tenofovir	Increased plasma tenofovir concentrations; unchanged plasma darunavir concentrations1 4 No in vitro evidence of antagonistic antiretroviral effects1	Manufacturer of darunavir recommends usual dosage of tenofovir with ritonavir-boosted darunavir 1 Some experts state clinical importance unknown; monitor for tenofovir toxicity4
Tipranavir	No in vitro evidence of antagonistic antiretroviral effects 1	Concomitant use not recommended1
Vardenafil	Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1	Do not exceed vardenafil dosage of 2.5 mg once every 72 hours; closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1 4
Zidovudine	Pharmacokinetic interaction unlikely1 No in vitro evidence of antagonistic antiretroviral effects1

Prezista Pharmacokinetics

Absorption

Bioavailability

Darunavir administered concomitantly with low-dose ritonavir (ritonavir-boosted darunavir).¹ Ritonavir decreases metabolism of darunavir, resulting in increased plasma darunavir concentrations.¹

Peak plasma darunavir concentrations attained approximately 2.5–4 hours after a dose.¹

Food

Compared with administration in the fasting state, administration of ritonavir-boosted darunavir with food increases peak darunavir concentrations and AUC approximately 30%.¹

Distribution

Extent

Not known whether distributed into human milk;¹ distributed into milk in rats.¹

Plasma Protein Binding

95%.¹

Binds principally to α₁-acid-glycoprotein.¹

Elimination

Metabolism

Darunavir extensively metabolized by CYP3A.¹

Elimination Route

Following administration of ritonavir-boosted darunavir, eliminated principally in feces as unchanged darunavir.¹ Approximately 80% of darunavir dose excreted in feces and 14% excreted in urine.¹

Half-life

15 hours.¹

Special Populations

Moderate renal impairment (Cl_cr 30–60 mL/minute): Pharmacokinetics not affected.¹

Severe renal impairment or end-stage renal disease: No pharmacokinetic data.¹

Unlikely to be removed by hemodialysis or peritoneal dialysis.¹

Hepatic impairment: Pharmacokinetics in individuals with mild hepatic impairment (Child-Pugh class A) or moderate hepatic impairment (Child-Pugh class B) similar to values in individuals with normal hepatic function.¹ Pharmacokinetics not evaluated in those with severe hepatic impairment.¹

HBV or HCV coinfection: No effect on darunavir exposure.¹

Higher darunavir concentrations reported in females compared with males; dosage adjustments not required.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Actions and SpectrumActions

• 
  

  Darunavir is administered in conjunction with low-dose ritonavir (ritonavir-boosted darunavir).¹

  
  


• 
  

  Darunavir is extensively metabolized by CYP3A; ritonavir is a potent inhibitor of CYP3A.¹ Concomitant use of these drugs results in decreased metabolism and increased plasma concentrations of darunavir.¹

  
  


• 
  

  Antiretroviral activity is due to darunavir.¹

  
  


• 
  

  Active against HIV-1.¹

  
  


• 
  

  Darunavir inhibits replication of HIV-1 by interfering with HIV proteases.¹

  
  


• 
  

  Darunavir-resistant HIV-1, including strains with decreased susceptibility to other PIs, has been reported.^{1 3}

  
  

Advice to Patients

• 
  

  Critical nature of compliance with HIV therapy.¹ Importance of using darunavir with low-dose ritonavir; importance of using these 2 drugs in conjunction with other antiretrovirals.¹

  
  


• 
  

  Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.¹ HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.¹

  
  


• 
  

  Importance of reading patient information provided by the manufacturer.¹

  
  


• 
  

  Importance of taking darunavir with food and at the same time as ritonavir.¹ Importance of swallowing the darunavir tablets whole with a drink (e.g., water, milk); the tablets should not be chewed.¹ If also taking didanosine, administer didanosine dose 1 hour before or 2 hours after ritonavir-boosted darunavir.¹

  
  


• 
  

  If a dose of darunavir or ritonavir is missed by <6 hours, administer the dose as soon as it is remembered and the next dose at the regularly scheduled time.¹ If a dose of darunavir or ritonavir is missed by >6 hours, omit the dose and administer the next dose at the regularly scheduled time.¹ Do not administer a double dose to make up for a missed dose.¹

  
  


• 
  

  Importance of patient informing their clinician if they are allergic to sulfonamides.¹

  
  


• 
  

  Redistribution/accumulation of body fat may occur with antiretroviral therapy, with as yet unknown long-term health effects.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products (e.g., St. John’s wort), and any concomitant illnesses.¹

  
  


• 
  

  Advise patients receiving selective phosphodiesterase (PDE) inhibitors (e.g., sildenafil, tadalafil, vardenafil) that they may be at increased risk of PDE inhibitor-associated adverse effects (e.g., hypotension, visual changes, priapism) and that any symptoms should be promptly reported to their clinician.¹

  
  


• 
  

  Importance of women using a reliable nonhormonal (e.g., barrier) method of contraception because of the potential interaction with hormonal contraceptives.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Darunavir (Ethanolate)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	75 mg (of darunavir)	Prezista	Tibotec
		150 mg (of darunavir)	Prezista	Tibotec
		400 mg (of darunavir)	Prezista	Tibotec
		600 mg (of darunavir)	Prezista	Tibotec

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Prezista 400MG Tablets (CENTOCOR ORTHO BIOTECH PRODUCT): 60/$1060.01 or 120/$2120.03

Prezista 600MG Tablets (CENTOCOR ORTHO BIOTECH PRODUCT): 60/$1100.02 or 180/$3109.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Tibotec. Prezista (darunavir) prescribing information. Raritan, NJ; 2008 Dec.

2. Koh Y, Nakata H, Maeda K et al. Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob Agents Chemother. 2003; 47:3123-9. [PubMed 14506019]

3. De Meyer S, Azijn H, Surleraux D et al. TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005; 49:2314-21. [PubMed 15917527]

4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (November 3, 2008). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().

5. Hammer SM, Saag MS, Schechter M, et al. Treatment of adult HIV infection: 2006 recommendations of the International AIDS Society–USA panel. JAMA. 2006; 296:827-43. [PubMed 16905788]

6. Banhegyi D, Esser S, Opravil M, Lefebvre E. TMC114/r outperforms investigator-selected PI(s) in treatment-experienced patients: 24-week primary efficacy and safety analysis of POWER 1. 1st European and Central Asian AIDS conference , Moscow, Russia, 2006 May 15–17. Poster. From Tibotec website ().

7. Perinatal HIV Guidelines Working Group. Public Health Service task force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States (April 29, 2009). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().

8. Working Group on Antiretroviral Therapy and Medical Management of HIV-infected Children of the National Resource Center at the François-Xavier Bagnoud Center, Health Resources and Services Administration (HRSA), and National Institutes of Health (NIH). Guidelines for the use of antiretroviral agents in pediatric HIV infection (February 23, 2009). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().

9. Madruga JV, Berger D, McMurchie M et al. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet. 2007; 370:49-58. [PubMed 17617272]

10. Ortiz R, DeJesus E, Khanlou H et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1 infected patients at week 48. AIDS. 2008; 22:1389-97. [PubMed 18614861]

11. Tibotec Therapeutics. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2008 Jan.

More Prezista resources

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

• Prezista Prescribing Information (FDA)


• Prezista Advanced Consumer (Micromedex) - Includes Dosage Information


• Prezista MedFacts Consumer Leaflet (Wolters Kluwer)


• Prezista Consumer Overview

Compare Prezista with other medications

• HIV Infection

Endospec

Endospec may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Endospec

Albendazole

Albendazole is reported as an ingredient of Endospec in the following countries:

• United Kingdom

International Drug Name Search

Ziac

Pronunciation: BIS-oh-PROE-lol/HYE-droe-KLOR-oh-THYE-a-zide
Generic Name: Bisoprolol/Hydrochlorothiazide
Brand Name: Ziac

Ziac is used for:

Treating high blood pressure.

Ziac is a beta-blocker and diuretic combination. The beta-blocker works by slowing down the heartbeat, helping the heart beat more regularly, and reducing the amount of work the heart has to do. The diuretic increases the elimination of excess fluid, which helps to decrease blood pressure.

Do NOT use Ziac if:

• you are allergic to any ingredient in Ziac or to a sulfonamide medicine (eg, sulfamethoxazole, probenecid, glyburide)


• you have uncontrolled heart failure, heart block, a very slow heart rate, or shock caused by serious heart problems


• you are unable to urinate


• you are taking another beta-blocker (eg, propranolol), dofetilide, or mibefradil

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

Before using Ziac:

Some medical conditions may interact with Ziac. 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 asthma, bronchitis, lung disease (eg, chronic obstructive pulmonary disease [COPD]), diabetes, gout, an overactive thyroid, low blood levels of potassium or sodium, blood vessel or circulation problems, an adrenal gland tumor (pheochromocytoma), lupus, liver disease, or kidney problems


• if you have low blood pressure or a history of chest pain or angina, heart attack, slow or irregular heartbeat, or other heart problems (eg, heart failure)


• if you will be having surgery or receiving anesthesia


• if you have recently had a certain type of nerve surgery (sympathectomy)

Some MEDICINES MAY INTERACT with Ziac. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Antiarrhythmics (eg, disopyramide, flecainide), calcium channel blockers (eg, verapamil, diltiazem), cimetidine, digoxin, fingolimod, or other medicines for blood pressure because side effects, such as slow or irregular heart beat or low blood pressure, may occur


• Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril), barbiturates (eg, phenobarbital), diazoxide, mefloquine, mibefradil, narcotics (eg, codeine), or nifedipine because the actions and side effects of Ziac and these medicines may be increased


• Adrenocorticotropic hormone (ACTH), other beta-blockers (eg, propranolol), corticosteroids (eg, prednisone), guanethidine, or reserpine because they may increase the risk of Ziac's side effects


• Cholestyramine, colestipol, nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen), or rifamycins (eg, rifampin) because they may decrease Ziac's effectiveness


• Allopurinol, amantadine, dofetilide, insulin or other medicines for diabetes (eg, glyburide), ketanserin, or lithium because their actions and the risk of their side effects may be increased


• Clonidine because stopping it or Ziac suddenly can lead to a rapid increase in blood pressure

This may not be a complete list of all interactions that may occur. Ask your health care provider if Ziac 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 Ziac:

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

• Take Ziac by mouth with or without food.


• If you also take cholestyramine or colestipol, ask your doctor or pharmacist how to take it with Ziac.


• Ziac may increase the amount of urine or cause you to urinate more often when you first start taking it. To keep this from disturbing your sleep, try to take your dose before 6 pm.


• Take Ziac on a regular schedule to get the most benefit from it.


• Continue to take Ziac even if you feel well. Do not miss any doses.


• If you miss a dose of Ziac, 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 Ziac.

Important safety information:

• Ziac may cause dizziness or light-headedness. These effects may be worse if you take it with alcohol or certain medicines. Use Ziac with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Ziac may cause dizziness, light-headedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.


• Drink plenty of fluids while taking Ziac and avoid engaging in activities that cause excessive sweating. Dehydration, excessive sweating, vomiting, or diarrhea may lead to a fall in blood pressure. Contact your health care provider at once if any of these occur.


• Ziac may decrease the amount of potassium in your body. If your doctor has also prescribed a potassium supplement for you, follow the dosing directions carefully. Check with your doctor before taking additional potassium on your own or including foods high in potassium (eg, bananas, orange juice) in your diet.


• Patients who take medicine for high blood pressure often feel tired or run down for a few weeks after starting treatment. Be sure to take your medicine even if you may not feel "normal." Tell your doctor if you develop any new symptoms.


• Ziac contains a sulfonamide called hydrochlorothiazide, which can cause certain eye problems (myopia, angle-closure glaucoma). Your risk may be increased if you are allergic to sulfonamide medicines (eg, sulfamethoxazole) or to penicillin antibiotics (eg, amoxicillin). Untreated angle-closure glaucoma can lead to permanent vision loss. If these eye problems occur, symptoms usually occur within hours to weeks of starting Ziac. Contact your doctor immediately if you experience symptoms such as vision changes (eg, decreased vision clearness) or eye pain.


• Do not suddenly stop taking Ziac. Sharp chest pain, irregular heartbeat, and sometimes heart attack may occur if you suddenly stop taking Ziac. The risk may be greater if you have certain types of heart disease. Your doctor should slowly lower your dose. When stopping treatment with Ziac, your doctor will need to slowly decrease your dose over a period of 1 to 2 weeks and will watch you closely for side effects. If new or worsened chest pain or other heart problems occur, contact your doctor right away. You may need to start taking Ziac again. Because heart artery disease is common and you may not know you have it, it may be safer not to stop Ziac quickly even if you are only being treated for high blood pressure.


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


• Tell your doctor or dentist that you take Ziac before you receive any medical or dental care, emergency care, or surgery.


• If you have high blood pressure, do not use nonprescription products that contain stimulants. These products may include diet pills or cold medicines. Contact your doctor if you have any questions or concerns.


• Diabetes patients - Ziac may hide signs of low blood sugar, such as a rapid heartbeat. Be sure to watch for other signs of low blood sugar. Low blood sugar may make you anxious, sweaty, weak, dizzy, drowsy, or faint. It may also make your vision change; give you a headache, chills, or tremors; or make you more hungry. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• If you have a history of any severe allergic reaction, talk with your doctor. You may be at risk of an even more severe allergic reaction if you come into contact with the substance that caused your allergy. Some medicines used to treat severe allergies may also not work as well while you are taking Ziac.


• Ziac may interfere with certain lab tests, including parathyroid function. Be sure your doctor and lab personnel know you are taking Ziac.


• Lab tests, including blood pressure, heart rate, and blood electrolytes, may be performed while you use Ziac. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Ziac with caution in the ELDERLY; they may be more sensitive to its effects.


• Ziac should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: It is not known if Ziac can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Ziac while you are pregnant. Ziac is found in breast milk. Do not breast-feed while taking Ziac.

Possible side effects of Ziac:

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:

Diarrhea; dizziness; headache; light-headedness; tiredness.

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; unusual hoarseness); chest pain; chills, fever, or sore throat; cold hands or feet; decreased urination; drowsiness; dry mouth or eyes; eye pain; fainting; mood or mental changes (eg, anxiety, decreased concentration, decreased memory, depression, hallucinations); muscle pain, cramps, or weakness; nausea; red, swollen, blistered, or peeling skin; restlessness; ringing in the ears or decreased hearing; severe or persistent dizziness or light-headedness; severe or persistent stomach pain; shortness of breath; slow, fast, or irregular heartbeat; sudden, unexplained weight gain; swelling of the hands, ankles, or feet; symptoms of low blood sodium levels (eg, confusion, seizures, sluggishness); unusual bruising or bleeding; unusual thirst, weakness, or fatigue; vision changes (eg, blurred vision, decreased vision clearness); vomiting; wheezing; yellowing of the skin or eyes.

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: Ziac 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. Symptoms may include fainting; loss of consciousness; severe dizziness or light-headedness; slow heart rate; symptoms of blood electrolyte problems (eg, confusion; irregular heartbeat; mental or mood changes; muscle pain, weakness, or cramping; seizures; sluggishness); symptoms of dehydration (eg, drowsiness; dry mouth or eyes; fast heartbeat; nausea or vomiting; unusual thirst, weakness, or fatigue); trouble breathing.

Proper storage of Ziac:

Store Ziac 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 Ziac out of the reach of children and away from pets.

General information:

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


• Ziac 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 Ziac. 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 Ziac resources

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

• Ziac Prescribing Information (FDA)


• Ziac Advanced Consumer (Micromedex) - Includes Dosage Information


• Ziac Consumer Overview

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