text:
Generic Name: didanosine pediatric powder for oral solution
Brand Name: Videx
Drug Class: HIV, NNRTIs
Last updated on RxList: 1/4/2019
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HIV and AIDS: Antiretroviral Drugs, Treatments and Medications
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Indications & Dosage
Warnings & Precautions
VIDEX®
(didanosine) Powder for Oral Solution
PANCREATITIS, LACTIC ACIDOSIS and HEPATOMEGALY with STEATOSIS
Fatal and nonfatal pancreatitis has occurred during therapy with VIDEX used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. VIDEX should be suspended in patients with suspected pancreatitis and discontinued in patients with confirmed pancreatitis [see WARNINGS AND PRECAUTIONS].
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. Coadministration of VIDEX and stavudine is contraindicated because of increased risk of serious and/or life-threatening events [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS]. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occurs.
VIDEX® is a brand name for didanosine, a synthetic purine nucleoside analogue active against HIV-1.
Didanosine is available as VIDEX, a Pediatric Powder for Oral Solution [see HOW SUPPLIED] and as VIDEX® EC Delayed-Release Capsules, containing enteric-coated beadlets [consult prescribing information for VIDEX EC (didanosine).
The chemical name for didanosine is 2',3'-dideoxyinosine. The structural formula is:
Didanosine is a white crystalline powder with the molecular formula C10H12N4O3 and a molecular weight of 236.2. The aqueous solubility of didanosine at 25° C and pH of approximately 6 is 27.3 mg per mL. Didanosine is unstable in acidic solutions. For example, at pH less than 3 and 37° C, 10% of didanosine decomposes to hypoxanthine in less than 2 minutes.
VIDEX® (didanosine, USP), also known as ddI, in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus (HIV)-1 infection [see Clinical Studies].
VIDEX should be administered on an empty stomach, at least 30 minutes before or 2 hours after eating.
Recommended Dosage (Adult And Pediatric Patients)
The preferred dosing frequency of VIDEX is twice daily because there is more evidence to support the effectiveness of this dosing regimen. Once-daily dosing should be considered only for patients whose management requires once-daily dosing of VIDEX [see Clinical Studies]. The recommended adult total daily dose is based on body weight (kg) (see Table 1).
Table 1: Recommended Dosage (Adult)
at least 60 kg less than 60 kg
Preferred dosing 200 mg twice daily 125 mg twice daily
Dosing for patients whose management requires once-daily frequency 400 mg once daily 250 mg once daily
Pediatric Patients (2 Weeks Old To 18 Years Old)
The recommended dose of VIDEX (didanosine) in pediatric patients between 2 weeks old and 8 months old is 100 mg per m2 twice daily, and the recommended VIDEX dose for pediatric patients greater than 8 months old is 120 mg per m2 twice daily but not to exceed the adult dosing recommendation.
Dosing recommendations in patients less than 2 weeks of age cannot be made because the pharmacokinetics of didanosine in these children are too variable to determine an appropriate dose. There are no data on once-daily dosing of VIDEX in pediatric patients.
Renal Impairment
In adult patients with impaired renal function, the dose of VIDEX should be adjusted to compensate for the slower rate of elimination. The recommended doses and dosing intervals of VIDEX in adult patients with renal insufficiency are presented in Table 2.
Table 2: Recommended Dosage in Patients with Renal Impairment
Creatinine Clearance (mL/min) Recommended VIDEX Dose by Patient Weight
at least 60 200 mg twice dailya 125 mg twice dailya
30-59 200 mg once daily or 100 mg twice daily 150 mg once daily or 75 mg twice daily
10-29 150 mg once daily 100 mg once daily
less than 10 100 mg once daily 75 mg once daily
a 400 mg once daily (at least 60 kg) or 250 mg once daily (less than 60 kg) for patients whose management requires once-daily frequency of administration.
Pediatric Patients
Urinary excretion is also a major route of elimination of didanosine in pediatric patients, therefore the clearance of didanosine may be altered in pediatric patients with renal impairment. Although there are insufficient data to recommend a specific dose adjustment of VIDEX in this patient population, a reduction in the dose should be considered (see Table 2).
Patients Requiring Continuous Ambulatory Peritoneal Dialysis (CAPD) Or Hemodialysis
For patients requiring CAPD or hemodialysis, follow dosing recommendations for patients with creatinine clearance of less than 10 mL per min, shown in Table 2. It is not necessary to administer a supplemental dose of VIDEX following hemodialysis.
Dosage Adjustment
Concomitant Therapy With Tenofovir Disoproxil Fumarate
In patients who are also taking tenofovir disoproxil fumarate, a dose reduction of VIDEX to 250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL per min) or 200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL per min) once daily is recommended. VIDEX and tenofovir disoproxil fumarate may be taken together in the fasted state. Alternatively, if tenofovir disoproxil fumarate is taken with food, VIDEX should be taken on an empty stomach (at least 30 minutes before food or 2 hours after food). The appropriate dose of VIDEX coadministered with tenofovir disoproxil fumarate in patients with creatinine clearance of less than 60 mL per min has not been established. ([see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]; see the complete prescribing information for VIDEX EC (enteric-coated formulation of didanosine) for results of drug interaction studies of tenofovir disoproxil fumarate with reduced doses of the enteric-coated formulation of didanosine.)
Hepatic Impairment
No dose adjustment is required in patients with hepatic impairment [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Instructions For Reconstitution
Prior to dispensing, the pharmacist must reconstitute dry powder with Purified Water, USP, to an initial concentration of 20 mg per mL and immediately mix the resulting solution with antacid to a final concentration of 10 mg per mL as follows:
20 mg Per mL Initial Solution
Reconstitute the product to 20 mg per mL by adding 100 mL or 200 mL of Purified Water, USP, to the 2 g or 4 g of VIDEX powder, respectively, in the product bottle.
10 mg Per mL Final Admixture
Immediately mix one part of the 20 mg per mL initial solution with one part of any commercially available antacid that contains as active ingredients aluminum hydroxide (400 mg per 5 mL), magnesium hydroxide (400 mg per 5 mL), and simethicone (40 mg per 5 mL) for a final dispensing concentration of 10 mg VIDEX per mL. For patient home use, the admixture should be dispensed in appropriately sized, flint-glass or plastic (HDPE, PET, or PETG) bottles with child-resistant closures.
Instruct the patient to shake the admixture thoroughly prior to use and to store the tightly closed container in the refrigerator.
The bottles of powder should be stored at 59° F to 86° F (15° C to 30° C). The VIDEX admixture may be stored up to 30 days in a refrigerator, 36° F to 46° F (2° C to 8° C). Discard any unused portion after 30 days.
VIDEX (didanosine, USP) Pediatric Powder for Oral Solution is supplied in 4- and 8-ounce glass bottles containing 2 g or 4 g of VIDEX, respectively.
VIDEX (didanosine, USP) Pediatric Powder for Oral Solution is supplied as shown in Table 15:
Table 15: VIDEX Pediatric Powder for Oral Solution
NDC NO. Packaging Information Product Quantity
0087-6632-41 One, 4-ounce glass, bottle per carton 2 g/bottle
Distributed by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA. Revised: Jan 2018
What is HIV? See Answer
The following serious adverse reactions are described below and elsewhere in the labeling:
Pancreatitis [see BOX WARNING, WARNINGS AND PRECAUTIONS]
Lactic acidosis/severe hepatomegaly with steatosis [see BOX WARNING, WARNINGS AND PRECAUTIONS]
Hepatic toxicity [see WARNINGS AND PRECAUTIONS]
Non-cirrhotic portal hypertension [see WARNINGS AND PRECAUTIONS]
Peripheral neuropathy [see WARNINGS AND PRECAUTIONS]
Retinal changes and optic neuritis [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
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.
Clinical Trials Experience In Adults
Selected clinical adverse reactions that occurred in adult patients in clinical studies with VIDEX are provided in Tables 3 and 4.
Table 3: Selected Clinical Adverse Reactions from Monotherapy Studies
Adverse Reactions Percent of Patients*
ACTG 116A ACTG 116B/117
n=197 zidovudine
n=212 VIDEX
n=304
Diarrhea 19 15 28 21
Peripheral Neurologic Symptoms/Neuropathy 17 14 20 12
Abdominal Pain 13 8 7 8
Rash/Pruritus 7 8 9 5
Pancreatitis 7 3 6 2
* The incidences reported included all severity grades and all reactions regardless of causality.
Table 4: Selected Clinical Adverse Reactions from Combination Studies
Adverse Reactions Percent of Patientsa,c
AI454-148b START 2b
VIDEX + stavudine + nelfinavir
n=482 zidovudine + lamivudine + nelfinavir
n=248 VIDEX + stavudine + indinavir
n=102 zidovudine + lamivudine + indinavir
Nausea 28 40 53 67
Peripheral Neurologic Symptoms/Neuropathy 26 6 21 10
Headache 21 30 46 37
Rash 13 16 30 18
Vomiting 12 14 30 35
Pancreatitis (see below) 1 * less than 1 *
a Percentages based on treated subjects.
b Median duration of treatment 48 weeks.
c The incidences reported included all severity grades and all reactions regardless of causality.
* This event was not observed in this study arm.
Pancreatitis resulting in death was observed in one patient who received VIDEX (didanosine) plus stavudine plus nelfinavir in Study AI454-148 and in one patient who received VIDEX plus stavudine plus indinavir in the START 2 study. In addition, pancreatitis resulting in death was observed in 2 of 68 patients who received VIDEX plus stavudine plus indinavir plus hydroxyurea in an ACTG clinical trial [see WARNINGS AND PRECAUTIONS].
The frequency of pancreatitis is dose related. In phase 3 studies, incidence ranged from 1% to 10% with doses higher than are currently recommended and from 1% to 7% with recommended dose.
Selected laboratory abnormalities in clinical studies with VIDEX are shown in Tables 5-7.
Table 5: Selected Laboratory Abnormalities from Monotherapy Studies
Parameter Percent of Patients
SGOT (AST) (greater than 5 x ULN) 9 4 7 6
SGPT (ALT) (greater than 5 x ULN) 9 6 6 6
Alkaline phosphatase (greater than 5 x ULN) 4 1 1 1
Amylase (at least 1.4 x ULN) 17 12 15 5
Uric acid (greater than 12 mg/dL) 3 1 2 1
ULN = upper limit of normal.
Table 6: Selected Laboratory Abnormalities from Combination Studies
Parameter Percent of Patientsa
n=248 VIDEX +
stavudine + indinavir
Bilirubin (greater than 2.6 x ULN) less than 1 less than 1 16 8
GGT (greater than 5 x ULN) NC NC 5 2
Lipase (greater than 2 x ULN) 7 2 5 5
Amylase (greater than 2 x ULN) NC NC 8 2
NC = Not Collected.
Table 7: Selected Laboratory Abnormalities from Combination Studies (All Grades)
Bilirubin 7 3 68 55
SGOT (AST) 42 23 53 20
SGPT (ALT) 37 24 50 18
GGT NC NC 28 12
Lipase 17 11 26 19
Amylase NC NC 31 17
Clinical Trials Experience In Pediatric Patients
In clinical trials, 743 pediatric patients between 2 weeks and 18 years of age have been treated with didanosine. Adverse reactions and laboratory abnormalities reported to occur in these patients were generally consistent with the safety profile of didanosine in adults.
In pediatric phase 1 studies, pancreatitis occurred in 2 of 60 (3%) patients treated at entry doses
below 300 mg per m2 per day and in 5 of 38 (13%) patients treated at higher doses. In study ACTG 152, pancreatitis occurred in none of the 281 pediatric patients who received didanosine 120 mg per m2 every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg per m2 every 12 hours in combination with zidovudine [see Clinical Studies].
Retinal changes and optic neuritis have been reported in pediatric patients.
The following adverse reactions have been identified during postapproval use of didanosine. Because they are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to VIDEX, or a combination of these factors.
Blood and Lymphatic System Disorders – anemia, leukopenia, and thrombocytopenia.
Body as a Whole – alopecia, anaphylactoid reaction, asthenia, chills/fever, pain.
Digestive Disorders – anorexia, dyspepsia, and flatulence.
Exocrine Gland Disorders – pancreatitis (including fatal cases) [see BOX WARNING, WARNINGS AND PRECAUTIONS], sialadenitis, parotid gland enlargement, dry mouth, and dry eyes.
Hepatobiliary Disorders – symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis [see BOX WARNING, WARNINGS AND PRECAUTIONS]; non-cirrhotic portal hypertension [see WARNINGS AND PRECAUTIONS]; hepatitis and liver failure.
Metabolic Disorders – diabetes mellitus, hypoglycemia, and hyperglycemia.
Musculoskeletal Disorders – myalgia (with or without increases in creatine kinase), rhabdomyolysis including acute renal failure and hemodialysis, arthralgia, and myopathy.
Ophthalmologic Disorders – retinal depigmentation and optic neuritis [see WARNINGS AND PRECAUTIONS].
Established Drug Interactions
Clinical recommendations based on the results of drug interaction studies are listed in Table 8. Pharmacokinetic results of drug interaction studies are shown in Tables 12 and 13 [see CONTRAINDICATIONS, CLINICAL PHARMACOLOGY].
Table 8: Established Drug Interactions with VIDEX
Drug Effect Clinical Comment
ciprofloxacin ↓ ciprofloxacin concentration Administer VIDEX at least 2 hours after or 6 hours before ciprofloxacin.
delavirdine ↓ delavirdine concentration Administer VIDEX 1 hour after delavirdine.
ganciclovir ↑ didanosine concentration If there is no suitable alternative to ganciclovir, then use in combination with VIDEX with caution. Monitor for didanosine-associated toxicity.
indinavir ↓ indinavir concentration Administer VIDEX 1 hour after indinavir.
methadone ↓ didanosine concentration Do not coadminister methadone with VIDEX pediatric powder due to significant decreases in didanosine concentrations. If coadministration of methadone and didanosine is necessary, the recommended formulation of didanosine is VIDEX EC. Patients should be closely monitored for adequate clinical response when VIDEX EC is coadministered with methadone, including monitoring for changes in HIV RNA viral load.
nelfinavir No interaction 1 hour after didanosine Administer nelfinavir 1 hour after VIDEX.
tenofovir disoproxil fumarate ↑ didanosine concentration A dose reduction of VIDEX to the following dosage once daily is recommended.a
250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL/min)
200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL/min)
VIDEX and tenofovir disoproxil fumarate may be taken together in the fasted state. If tenofovir disoproxil fumarate is taken with food, VIDEX should be taken on an empty stomach (at least 30 minutes before food or 2 hours after food). Patients should be monitored for didanosineassociated toxicities and clinical response.
↑ Indicates increase.
↓ Indicates decrease.
a The dosing recommendation for coadministration of VIDEX EC and tenofovir disoproxil fumarate with respect to meal consumption differs from that of VIDEX. See the complete prescribing information for VIDEX EC.
Exposure to didanosine is increased when coadministered with tenofovir disoproxil fumarate [see CLINICAL PHARMACOLOGY]. Increased exposure may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. Coadministration of tenofovir disoproxil fumarate with VIDEX should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities and clinical response. VIDEX should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS]. Suppression of CD4 cell counts has been observed in patients receiving tenofovir disoproxil fumarate with didanosine at a dose of 400 mg daily.
Predicted Drug Interactions
Predicted drug interactions with VIDEX are listed in Table 9.
Table 9: Predicted Drug Interactions with VIDEX
Drug or Drug Class Effect Clinical Comment
Drugs that may cause pancreatic toxicity ↑ risk of pancreatitis Use only with extreme cautiona
Neurotoxic drugs ↑ risk of neuropathy Use with cautionb
Antacids containing magnesium or aluminum ↑ side effects associated with antacid components Use caution with VIDEX Pediatric Powder for Oral Solution
Azole antifungals ↓ ketoconazole or itraconazole concentration Administer drugs such as ketoconazole or itraconazole at least 2 hours before VIDEX.
Quinolone antibiotics (see also ciprofloxacin in Table 8) ↓ quinolone concentration Consult package insert of the quinolone.
Tetracycline antibiotics ↓ antibiotic concentration Consult package insert of the tetracycline.
Hydroxyurea ↑ risk of pancreatitis, fatal hepatotoxicity, and severe peripheral neuropathy Use should be avoided.
a Only if other drugs are not available and if clearly indicated. If treatment with life-sustaining drugs that cause pancreatic toxicity is required, suspension of VIDEX is recommended [see WARNINGS AND PRECAUTIONS].
b [See WARNINGS AND PRECAUTIONS]
Included as part of the "PRECAUTIONS" Section
Fatal and nonfatal pancreatitis has occurred during therapy with VIDEX used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. VIDEX should be suspended in patients with signs or symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Coadministration of VIDEX with stavudine is contraindicated [see CONTRAINDICATIONS].
When treatment with life-sustaining drugs known to cause pancreatic toxicity is required, suspension of VIDEX (didanosine) therapy is recommended. In patients with risk factors for pancreatitis, VIDEX should be used with extreme caution and only if clearly indicated. Patients with advanced HIV-1 infection, especially the elderly, are at increased risk of pancreatitis and should be followed closely. Patients with renal impairment may be at greater risk for pancreatitis if treated without dose adjustment. The frequency of pancreatitis is dose related [see ADVERSE REACTIONS].
Lactic Acidosis/Severe Hepatomegaly With Steatosis
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. Coadministration of VIDEX and stavudine is contraindicated [see CONTRAINDICATIONS and Use In Specific Populations]. Particular caution should be exercised when administering VIDEX to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with VIDEX should be suspended in any patient who develops clinical signs or symptoms with or without laboratory findings consistent with symptomatic hyperlactatemia, lactic acidosis, or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Hepatic Toxicity
The safety and efficacy of VIDEX have not been established in HIV-infected patients with significant underlying liver disease. During combination antiretroviral therapy, patients with preexisting liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities, including severe and potentially fatal hepatic adverse events, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Hepatotoxicity and hepatic failure resulting in death were reported during postmarketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. Coadministration of VIDEX and stavudine is contraindicated; the combination of VIDEX and hydroxyurea should be avoided [see CONTRAINDICATIONS, ADVERSE REACTIONS, and DRUG INTERACTIONS].
Non-Cirrhotic Portal Hypertension
Postmarketing cases of non-cirrhotic portal hypertension have been reported, including cases leading to liver transplantation or death. Cases of didanosine-associated non-cirrhotic portal hypertension were confirmed by liver biopsy in patients with no evidence of viral hepatitis. Onset of signs and symptoms ranged from months to years after start of didanosine therapy. Common presenting features included elevated liver enzymes, esophageal varices, hematemesis, ascites, and splenomegaly.
Patients receiving VIDEX should be monitored for early signs of portal hypertension (eg, thrombocytopenia and splenomegaly) during routine medical visits. Appropriate laboratory testing including liver enzymes, serum bilirubin, albumin, complete blood count, and international normalized ratio (INR) and ultrasonography should be considered. VIDEX should be discontinued in patients with evidence of non-cirrhotic portal hypertension.
Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in patients receiving VIDEX therapy. Peripheral neuropathy has occurred more frequently in patients with advanced HIV disease, in patients with a history of neuropathy, or in patients being treated with neurotoxic drug therapy. Discontinuation of VIDEX should be considered in patients who develop peripheral neuropathy [see CONTRAINDICATIONS, ADVERSE REACTIONS, and DRUG INTERACTIONS].
Retinal Changes And Optic Neuritis
Retinal changes and optic neuritis have been reported in adult and pediatric patients. Periodic retinal examinations should be considered for patients receiving VIDEX [see ADVERSE REACTIONS].
Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including VIDEX. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barre syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
Lipoatrophy
Treatment with VIDEX has been associated with loss of subcutaneous fat, which is most evident in the face, limbs, and buttocks. The incidence and severity of lipoatrophy are related to cumulative exposure, and is often not reversible when VIDEX treatment is stopped. Patients receiving VIDEX should be frequently examined and questioned for signs of lipoatrophy, and if feasible therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy.
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Advise patients that a serious toxicity of VIDEX, used alone and in combination regimens, is pancreatitis, which may be fatal. VIDEX is contraindicated in combination with stavudine [see WARNINGS AND PRECAUTIONS]. Closely monitor patients for symptoms of pancreatitis.
Lactic Acidosis And Severe Hepatomegaly With Steatosis
Advise patients that lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals [see WARNINGS AND PRECAUTIONS].
Inform patients that hepatotoxicity, including fatal hepatic adverse events, has been reported. The safety and efficacy of VIDEX have not been established in HIV-infected patients with significant underlying liver disease. VIDEX is contraindicated in combination with stavudine [see CONTRAINDICATIONS]. Avoid the combination of VIDEX with hydroxyurea [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].
Inform patients that non-cirrhotic portal hypertension has been reported in patients taking VIDEX, including cases leading to liver transplantation or death [see WARNINGS AND PRECAUTIONS].
Inform patients that peripheral neuropathy, manifested by numbness, tingling, or pain in hands or feet, may develop during therapy with VIDEX. Patients should be counseled that peripheral neuropathy occurs with greatest frequency in patients with advanced HIV-1 disease or a history of peripheral neuropathy, and that discontinuation of VIDEX may be required if toxicity develops [see WARNINGS AND PRECAUTIONS].
Inform patients that retinal changes and optic neuritis, which may result in blurred vision, have been reported in adult and pediatric patients. Advise patients to have regular eye exams while taking VIDEX [see WARNINGS AND PRECAUTIONS].
Advise patients to inform their healthcare provider immediately of any symptoms of infection, as in some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started [see WARNINGS AND PRECAUTIONS].
Inform patient that loss of body fat (e.g., from arms, legs, or face) may occur in individuals receiving antiretroviral therapy including VIDEX. Monitor patients receiving VIDEX to monitor for clinical signs and symptoms of lipoatrophy. Patients should be routinely questioned about body changes related to lipoatrophy [see WARNINGS AND PRECAUTIONS].
VIDEX may interact with many drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription of non-prescription medication or herbal products, including alcohol, which may exacerbate VIDEX toxicities [see CONTRAINDICATIONS, DRUG INTERACTIONS].
Pregnancy Registry
Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes of pregnancy women exposed to VIDEX [see Use In Specific Populations].
Inform patients that it is not known if VIDEX can be passed to the baby by breast milk and whether it could harm the baby. Advise mothers with HIV-1 not breastfeed because HIV-1 can be passed to the baby in breast milk [see Use In Specific Populations].
Dosing Information
Instruct patients to take VIDEX on an empty stomach at least 30 minutes before or 2 hours after eating.
Instruct patients that the preferred dosing frequency of VIDEX is twice daily because there is more evidence to support the effectiveness of this dosing frequency. Once-daily dosing should be considered only for patients whose management requires once-daily dosing of VIDEX.
Instruct patients not to miss a dose but if they do, patients should take VIDEX as soon as possible. Inform patients that it is important to take VIDEX on a regular dosing schedule and to avoid missing doses as it can result in development of resistance.
Nonclinical Toxicology
Lifetime carcinogenicity studies were conducted in mice and rats for 22 and 24 months, respectively. In the mouse study, initial doses of 120, 800, and 1200 mg per kg per day for each sex were lowered after 8 months to 120, 210, and 210 mg per kg per day for females and 120, 300, and 600 mg per kg per day for males. The two higher doses exceeded the maximally tolerated dose in females and the high dose exceeded the maximally tolerated dose in males. The low dose in females represented 0.68-fold maximum human exposure and the intermediate dose in males represented 1.7-fold maximum human exposure based on relative AUC comparisons. In the rat study, initial doses were 100, 250, and 1000 mg per kg per day, and the high dose was lowered to 500 mg per kg per day after 18 months. The upper dose in male and female rats represented 3-fold maximum human exposure.
Didanosine induced no significant increase in neoplastic lesions in mice or rats at maximally tolerated doses.
Didanosine was positive in the following genetic toxicology assays: 1) the Escherichia coli tester strain WP2 uvrA bacterial mutagenicity assay; 2) the L5178Y/TK+/- mouse lymphoma mammalian cell gene mutation assay; 3) the in vitro chromosomal aberrations assay in cultured human peripheral lymphocytes; 4) the in vitro chromosomal aberrations assay in Chinese Hamster Lung cells; and 5) the BALB/c 3T3 in vitro transformation assay. No evidence of mutagenicity was observed in an Ames Salmonella bacterial mutagenicity assay or in rat and mouse in vivo micronucleus assays.
Pregnancy Category B
Reproduction studies have been performed in rats and rabbits at doses up to 12 and 14.2 times the estimated human exposure (based upon plasma levels), respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to didanosine. At approximately 12 times the estimated human exposure, didanosine was slightly toxic to female rats and their pups during mid and late lactation. These rats showed reduced food intake and body weight gains but the physical and functional development of the offspring was not impaired and there were no major changes in the F2 generation. A study in rats showed that didanosine and/or its metabolites are transferred to the fetus through the placenta. Animal reproduction studies are not always predictive of human response.
There are no adequate and well-controlled studies of didanosine in pregnant women. Didanosine should be used during pregnancy only if the potential benefit justifies the potential risk.
Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. It is unclear if pregnancy augments the risk of lactic acidosis/hepatic steatosis syndrome reported in nonpregnant individuals receiving nucleoside analogues [see WARNINGS AND PRECAUTIONS]. The combination of VIDEX and stavudine is contraindicated [see CONTRAINDICATIONS]. Healthcare providers caring for HIVinfected pregnant women receiving didanosine should be alert for early diagnosis of lactic acidosis/hepatic steatosis syndrome.
Antiretroviral Pregnancy Registry
To monitor maternal-fetal outcomes of pregnant women exposed to didanosine and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. A study in rats showed that following oral administration, didanosine and/or its metabolites were excreted into the milk of lactating rats. It is not known if didanosine is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving didanosine.
Use of didanosine in pediatric patients from 2 weeks of age through adolescence is supported by evidence from adequate and well-controlled studies of VIDEX in adult and pediatric patients [see DOSAGE AND ADMINISTRATION, ADVERSE REACTIONS, CLINICAL PHARMACOLOGY, Clinical Studies].
In an Expanded Access Program for patients with advanced HIV infection, patients aged 65 years and older had a higher frequency of pancreatitis (10%) than younger patients (5%) [see WARNINGS AND PRECAUTIONS]. Clinical studies of didanosine did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently than younger subjects. Didanosine is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. In addition, renal function should be monitored and dosage adjustments should be made accordingly [see DOSAGE AND ADMINISTRATION].
Patients with renal impairment (creatinine clearance of less than 60 mL per min) may be at greater risk of toxicity from didanosine due to decreased drug clearance [see CLINICAL PHARMACOLOGY]. A dose reduction is recommended for these patients [see DOSAGE AND ADMINISTRATION].
There is no known antidote for VIDEX (didanosine) overdosage. In phase 1 studies, in which VIDEX was initially administered at doses ten times the currently recommended dose, toxicities included: pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia, and hepatic dysfunction. Didanosine is not dialyzable by peritoneal dialysis, although there is some clearance by hemodialysis [see CLINICAL PHARMACOLOGY].
Videx is contraindicated when coadministered with the following medications:
Coadministration of didanosine and stavudine is contraindicated because of the potential for serious and/or life-threatening events notably pancreatitis, lactic acidosis, hepatotoxicity, and peripheral neuropathy [see WARNINGS AND PRECAUTIONS].
Coadministration of didanosine and allopurinol is contraindicated because systemic exposures of didanosine are increased, which may increase didanosine-associated toxicity [see CLINICAL PHARMACOLOGY].
Coadministration of didanosine and ribavirin is contraindicated because exposures of the active metabolite of didanosine (dideoxyadenosine 5'-triphosphate) are increased. Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving both didanosine and ribavirin.
Didanosine is an antiretroviral drug [see Microbiology].
The pharmacokinetic parameters of didanosine are summarized in Table 10. Didanosine is rapidly absorbed, with peak plasma concentrations generally observed from 0.25 to 1.50 hours following oral dosing. Increases in plasma didanosine concentrations were dose proportional over the range of 50 to 400 mg. Steady-state pharmacokinetic parameters did not differ significantly from values obtained after a single dose. Binding of didanosine to plasma proteins in vitro was low (less than 5%). Based on data from in vitro and animal studies, it is presumed that the metabolism of didanosine in man occurs by the same pathways responsible for the elimination of endogenous purines.
Table 10: Mean ± SD Pharmacokinetic Parameters for Didanosine in Adult and Pediatric Patients
Parameter Adult Patientsa n Pediatric Patientsb
n 8 months to 19 years 2 weeks to 4 months n
Oral bioavailability (%) 42 ± 12 6 25 ± 20 46 ND
Apparent volume of distributionc (L/m2) 43.70 ± 8.90 6 28 ± 15 49 ND
CSF-plasma ratiod 21 ± 0.03%e 5 46% (range 12-85%) 7 ND
Systemic clearancec (mL/min/m2) 526 ± 64.7 6 516 ± 184 49 ND
Renal clearancef (mL/min/m2) 223 ± 85.0 6 240 ± 90 15 ND
Apparent oral clearanceg (mL/min/m2) 1252 ± 154 6 2064 ± 736 48 1353 ± 759 41
Elimination half-lifef (h) 1.5 ± 0.4 6 0.8 ± 0.3 60 1.2 ± 0.3 21
Urinary recovery of didanosinef (%) 18 ± 8 6 18 ± 10 15 ND
CSF = cerebrospinal fluid, ND = not determined.
a Parameter units for adults were converted to the same units in pediatric patients to facilitate comparisons among populations: mean adult body weight = 70 kg and mean adult body surface area = 1.73 m2.
b In 1-day old infants (n=10), the mean ± SD apparent oral clearance was 1523 ± 1176 mL/min/m2 and half-life was 2.0 ± 0.7 h.
c Following IV administration.
d Following IV administration in adults and IV or oral administration in pediatric patients.
e Mean ± SE.
f Following oral administration.
g Apparent oral clearance estimate was determined as the ratio of the mean systemic clearance and the mean oral bioavailability estimate.
Effect Of Food
Didanosine peak plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) were decreased by approximately 55% when VIDEX tablets were administered up to 2 hours after a meal. Administration of VIDEX tablets up to 30 minutes before a meal did not result in any significant changes in bioavailability [see DOSAGE AND ADMINISTRATION]. VIDEX should be taken on an empty stomach.
Renal Insufficiency
Data from two studies in adults indicated that the apparent oral clearance of didanosine decreased and the terminal elimination half-life increased as creatinine clearance decreased (see Table 11). Following oral administration, didanosine was not detectable in peritoneal dialysate fluid (n=6); recovery in hemodialysate (n=5) ranged from 0.6% to 7.4% of the dose over a 3-4 hour dialysis period. The absolute bioavailability of didanosine was not affected in patients requiring dialysis [See DOSAGE AND ADMINISTRATION].
Table 11: Mean ± SD Pharmacokinetic Parameters for Didanosine Following a Single Oral Dose
Parameter Creatinine Clearance (mL/min) Dialysis Patients n=11
at least 90
n=12 60-90
n=6 30-59
n=3
CLcr (mL/min) 112 ± 22 68 ± 8 46 ± 8 13 ± 5 ND
CL/F (mL/min) 2164 ± 638 1566 ± 833 1023 ± 378 628 ± 104 543 ± 174
CLR (mL/min) 458 ± 164 247 ± 153 100 ± 44 20 ± 8 less than 10
T½ (h) 1.42 ± 0.33 1.59 ± 0.13 1.75 ± 0.43 2.0 ± 0.3 4.1 ± 1.2
ND = not determined due to anuria.
CLcr = creatinine clearance.
CL/F = apparent oral clearance.
CLR = renal clearance.
The pharmacokinetics of didanosine have been studied in 12 non-HIVinfected subjects with moderate (n=8) to severe (n=4) hepatic impairment (Child-Pugh Class B or C). Mean AUC and Cmax values following a single 400 mg dose of didanosine were approximately 13% and 19% higher, respectively, in patients with hepatic impairment compared to matched healthy subjects. No dose adjustment is needed, because a similar range and distribution of AUC and Cmax values was observed for subjects with hepatic impairment and matched healthy controls. [See DOSAGE AND ADMINISTRATION].
The pharmacokinetics of didanosine have been evaluated in HIV-exposed and HIV-infected pediatric patients from birth to adulthood. Overall, the pharmacokinetics of didanosine in pediatric patients are similar to those of didanosine in adults. Didanosine plasma concentrations appear to increase in proportion to oral doses ranging from 25 to 120 mg per m2 in pediatric patients less than 5 months old and from 80 to 180 mg per m2 in children above 8 months old. For information on controlled clinical studies in pediatric patients, [see Clinical Studies and Use In Specific Populations].
Didanosine pharmacokinetics have not been studied in patients over 65 years of age [see Use In Specific Populations].
The effects of gender on didanosine pharmacokinetics have not been studied.
Tables 12 and 13 summarize the effects on AUC and Cmax, with a 95% confidence interval (CI) when available, following coadministration of VIDEX (didanosine) with a variety of drugs. Drug-drug interactions for VIDEX buffered tablets are applicable to the VIDEX pediatric powder formulation and are noted in Tables 12 and 13. For clinical recommendations based on drug interaction studies for drugs in bold font, see DOSAGE AND ADMINISTRATION ( for Concomitant Therapy With Tenofovir Disoproxil Fumarate), CONTRAINDICATIONS , and DRUG INTERACTIONS.
Table 12: Results of Drug Interaction Studies with VIDEX: Effects of Coadministered Drug on Didanosine Plasma AUC and Cmax Values
Drug Didanosine Dosage n % Change of Didanosine Pharmacokinetic Parametersa
AUC of Didanosine
(95% CI) Cmax of Didanosine
(95% CI)
allopurinol, renally impaired, 300 mg/day 200 mg single dose 2 ↑ 312% ↑ 232%
healthy volunteer, 300 mg/day for 7 days 400 mg single dose 14 ↑ 113% ↑ 69%
ciprofloxacin, 750 mg every 12 hours for 3 days, 2 hours before didanosine 200 mg every 12 hours for 3 days 8b ↓ 16% ↓ 28%
ganciclovir, 1000 mg every 8 hours, 2 hours after didanosine 200 mg every 12 hours 12 ↑ 111% NA
indinavir, 800 mg single dose, simultaneous 200 mg single dose 16 ↔ ↔
1 hour before didanosine 200 mg single dose 16 ↓ 17%
(-27, -7%)c ↓ 13%
(-28, 5%)c
ketoconazole, 200 mg/day for 4 days, 2 hours before didanosine 375 mg every 12 hours for 4 days 12b ↔ ↓ 12%
methadone, chronic maintenance dosef 200 mg single dose 16d ↓ 57% ↓ 66%
400 mg single dose 15, 16e ↓ 29%
(-40, -16%)c ↓ 41%
(-54, -26%)c
tenofovir,g,h 300 mg once daily, 1 hour after didanosine 250i mg or 400 mg once daily for 7 days 14 ↑ 44%
(31, 59%)c ↑ 28%
(11, 48%)c
loperamide, 4 mg every 6 hours for 1 day 300 mg single dose 12b ↔ ↓ 23%
metoclopramide, 10 mg single dose 300 mg single dose 12b ↔ ↑ 13%
ranitidine, 150 mg single dose, 2 hours before didanosine 375 mg single dose 12b ↑ 14% ↑ 13%
rifabutin, 300 or 600 mg/day for 12 days 167 mg or 250 mg every 12 hours for 12 days 11 ↑ 13%
(-1, 27%) ↑ 17%
(-4, 38%)
ritonavir, 600 mg every 12 hours for 4 days 200 mg every 12 hours for 4 days 12 ↓ 13%
(0, 23%) ↓ 16%
(5, 26%)
stavudine, 40 mg every 12 hours for 4 days 100 mg every 12 hours for 4 days 10 ↔ ↔
sulfamethoxazole, 1000 mg single dose 200 mg single dose 8b ↔ ↔
trimethoprim, 200 mg single dose 200 mg single dose 8b ↔ ↑ 17%
(-23, 77%)
zidovudine, 200 mg every 8 hours for 3 days 200 mg every 12 hours for 3 days 6b ↔ ↔
↔ Indicates no change, or mean increase or decrease of less than 10%.
a The 95% confidence intervals for the percent change in the pharmacokinetic parameter are displayed.
b HIV-infected patients.
c 90% CI.
d Comparisons are made to a parallel control group not receiving methadone (n=10).
e Comparisons are made to historical controls (n=68, pooled from 3 studies) conducted in healthy subjects. The number of subjects evaluated for AUC and Cmax is 15 and 16, respectively.
f For results of drug interaction studies between the enteric-coated formulation of didanosine (VIDEX EC) and methadone, see the complete prescribing information for VIDEX EC.
g Tenofovir disoproxil fumarate.
h For results of drug interaction studies between the enteric-coated formulation of didanosine (VIDEX EC) and tenofovir disoproxil fumarate, see the complete prescribing information for VIDEX EC.
i Patients less than 60 kg with creatinine clearance of at least 60 mL/min.
NA = Not available.
Table 13: Results of Drug Interaction Studies with VIDEX: Effects of Didanosine on Coadministered Drug Plasma AUC and Cmax Values
Drug Didanosine Dosage n % Change of Coadministered Drug Pharmacokinetic Parametersa
AUC of Coadministered Drug
(95% CI) Cmax of Coadministered Drug
750 mg single dose buffered placebo tablet 12 ↓ 98% ↓ 93%
delavirdine, 400 mg single dose 125 mg or 200 mg every 12 hours 12b ↓ 32% ↓ 53%
simultaneous 1 hour before didanosine 125 mg or 200 mg every 12 hours 12b ↑ 20% ↑ 18%
ganciclovir, 1000 mg every 8 hours, 2 hours after didanosine 200 mg every 12 hours 12b ↓ 21% NA
indinavir, 800 mg single dose simultaneous 200 mg single dose 16 ↓ 84% ↓ 82%
1 hour before didanosine 200 mg single dose 16 ↓ 11% ↓ 4%
ketoconazole, 200 mg/day for 4 days, 2 hours before didanosine 375 mg every 12 hours for 4 days 12b ↓ 14% ↓ 20%
nelfinavir, 750 mg single dose, 1 hour after didanosine 200 mg single dose 10b ↑ 12% ↔
dapsone, 100 mg single dose 200 mg every 12 hours for 14 days 6b ↔ ↔
ranitidine, 150 mg single dose, 2 hours before didanosine 375 mg single dose 12b ↓ 16% ↔
ritonavir, 600 mg every 12 hours for 4 days 200 mg every 12 hours for 4 days 12 ↔ ↔
stavudine, 40 mg every 12 hours for 4 days 100 mg every 12 hours for 4 days 10b ↔ ↑ 17%
sulfamethoxazole, 1000 mg single dose 200 mg single dose 8b ↓ 11% (-17, -4%) ↓ 12% (-28, 8%)
tenofovir,c 300 mg once daily 1 hour after didanosine 250d mg or 400 mg once daily for 7 days 14 ↔ ↔
trimethoprim, 200 mg single dose 200 mg single dose 8b ↑ 10% (-9, 34%) ↓ 22% (-59, 49%)
zidovudine, 200 mg every 8 hours for 3 days 200 mg every 12 hours for 3 days 6b ↓ 10% (-27, 11%) ↓ 16.5% (-53, 47%)
a The 95% confidence intervals for the percent change in the pharmacokinetic parameter are displayed. b HIV-infected patients.
c Tenofovir disoproxil fumarate.
d Patients less than 60 kg with creatinine clearance of at least 60 mL/min.
Didanosine is a synthetic nucleoside analogue of the naturally occurring nucleoside deoxyadenosine in which the 3'-hydroxyl group is replaced by hydrogen. Intracellularly, didanosine is converted by cellular enzymes to the active metabolite, dideoxyadenosine 5'-triphosphate. Dideoxyadenosine 5'-triphosphate inhibits the activity of HIV-1 reverse transcriptase both by competing with the natural substrate, deoxyadenosine 5'-triphosphate, and by its incorporation into viral DNA causing termination of viral DNA chain elongation.
Antiviral Activity In Cell Culture
The anti-HIV-1 activity of didanosine was evaluated in a variety of HIV-1 infected lymphoblastic cell lines and monocyte/macrophage cell cultures. The concentration of drug necessary to inhibit viral replication by 50% (EC50) ranged from 2.5 to 10 μM (1 μM = 0.24 μg/mL) in lymphoblastic cell lines and 0.01 to 0.1 μM in monocyte/macrophage cell cultures.
HIV-1 isolates with reduced sensitivity to didanosine have been selected in cell culture and were also obtained from patients treated with didanosine. Genetic analysis of isolates from didanosinetreated patients showed amino acid substitutions K65R, L74V, and M184V in reverse transcriptase. The L74V substitution was most frequently observed in clinical isolates. Phenotypic analysis of HIV-1 isolates from 60 patients (some with prior zidovudine treatment) receiving 6 to 24 months of didanosine monotherapy showed that isolates from 10 of 60 patients exhibited an average of a 10-fold decrease in susceptibility to didanosine in cell culture compared to baseline isolates. Clinical isolates that exhibited a decrease in didanosine susceptibility harbored one or more didanosine resistance-associated substitutions.
Cross-Resistance
HIV-1 isolates from 2 of 39 patients receiving combination therapy for up to 2 years with didanosine and zidovudine exhibited decreased susceptibility to didanosine, lamivudine, stavudine, and zidovudine in cell culture. These isolates harbored five substitutions (A62V, V75I, F77L, F116Y, and Q151M) in reverse transcriptase. In data from clinical studies, the presence of thymidine analogue mutation substitutions (M41L, D67N, L210W, T215Y, K219Q) has been shown to decrease the response to didanosine.
Animal Toxicology And/Or Pharmacology
Evidence of a dose-limiting skeletal muscle toxicity has been observed in mice and rats (but not in dogs) following long-term (greater than 90 days) dosing with didanosine at doses that were approximately 1.2 to 12 times the estimated human exposure. The relationship of this finding to the potential of VIDEX (didanosine) to cause myopathy in humans is unclear. However, human myopathy has been associated with administration of VIDEX and other nucleoside analogues.
START 2 was a multicenter, randomized, open-label study comparing VIDEX (200 mg twice daily)/stavudine/indinavir to zidovudine/lamivudine/indinavir in 205 treatment-naive patients. Both regimens resulted in a similar magnitude of suppression of HIV-1 RNA levels and increases in CD4 cell counts through 48 weeks.
Study AI454-148 was a randomized, open-label, multicenter study comparing treatment with VIDEX (400 mg once daily) plus stavudine (40 mg twice daily) and nelfinavir (750 mg three times daily) versus zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily) and nelfinavir (750 mg three times daily) in 756 treatment-naive patients, with a median CD4 cell count of 340 cells per mm3 (range 80 to 1568 cells per mm3) and a median plasma HIV-1 RNA of 4.69 log10 copies per mL (range 2.6 to 5.9 log10 copies per mL) at baseline. Median CD4 cell count increases at 48 weeks were 188 cells per mm3 in both treatment groups. Treatment response and outcomes through 48 weeks are shown in Figure 1 and Table 14.
Figure 1: Treatment Response Through Week 48*, AI454-148
Table 14: Outcomes of Randomized Treatment Through Week 48, AI454-148
Week 48 Status Percent of Patients with HIV-1 RNA less than 400 copies/mL (less than 50 copies/mL)
VIDEX/ stavudine/nelfinavir
n=503 lamivudine/ zidovudine/nelfinavir
Respondera 50* (34*) 59 (47)
Virologic failureb 36 (57) 32 (48)
Death or disease progression less than 1 (less than 1) 1 (less than 1)
Discontinued due to adverse events 4 (2) 2 (less than 1)
Discontinued due to other reasonsc 6 (3) 4 (2)
Never initiated treatment 4 (4) 2 (2)
* p less than 0.05 for the differences between treatment groups, by Cochran-Mantel-Haenszel test.
a Patients achieved virologic response [two consecutive viral loads less than 400 (less than 50) copies/mL] and
maintained it to Week 48.
b Includes viral rebound and failing to achieve confirmed less than 400 (less than 50) copies/mL by Week 48.
c Includes lost to follow-up, noncompliance, withdrawal, and pregnancy.
Monotherapy
The efficacy of VIDEX was demonstrated in two randomized, double-blind studies comparing VIDEX, given on a twice-daily schedule, to zidovudine, given three times daily, in 617 (ACTG 116A, conducted 1989-1992) and 913 (ACTG 116B/117, conducted 1989-1991) patients with symptomatic HIV infection or AIDS who were treated for more than one year. In treatmentnaive patients (ACTG 116A), the rate of HIV disease progression or death was similar between the treatment groups; mortality rates were 26% for patients receiving VIDEX and 21% for patients receiving zidovudine. Of the patients who had received previous zidovudine treatment (ACTG 116B/117), those treated with VIDEX had a lower rate of HIV disease progression or death (32%) compared to those treated with zidovudine (41%); however, survival rates were similar between the treatment groups.
Studies have demonstrated that the clinical benefit of monotherapy with antiretrovirals, including VIDEX, was time limited.
Efficacy in pediatric patients was demonstrated in a randomized, double-blind, controlled study (ACTG 152, conducted 1991-1995) involving 831 patients 3 months to 18 years of age treated for more than 1.5 years with zidovudine (180 mg per m2 every 6 hours), VIDEX (120 mg per m2 every 12 hours), or zidovudine (120 mg per m2 every 6 hours) plus VIDEX (90 mg per m2 every 12 hours). Patients treated with VIDEX or VIDEX plus zidovudine had lower rates of HIV-1 disease progression or death compared with those treated with zidovudine alone.
(VY-dex)
(didanosine, USP) Powder for Oral Solution
What is the most important information I should know about VIDEX?
VIDEX can cause serious side effects, including:
Inflammation of your pancreas (pancreatitis) can happen in people who take VIDEX and can lead to death. People who take VIDEX in combination with the medicine stavudine may be at an increased risk for pancreatitis. Do not take VIDEX with stavudine.
Call your healthcare provider right away if you have any of the following symptoms of pancreatitis:
severe stomach (abdomen) pain
swelling of your stomach
Build-up of an acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take VIDEX or similar medicines (nucleoside analogues). Lactic acidosis is a serious medical emergency that can lead to death. There have been deaths reported in pregnant women who get lactic acidosis after taking VIDEX and ZERIT (stavudine). Do not take VIDEX with stavudine.
Call your healthcare provider right away if you have any of the following symptoms which could be signs of lactic acidosis:
feel very weak or tired
feel cold, especially in your arms and legs
have unusual (not normal) muscle pain
feel dizzy or light-headed
have trouble breathing
have a fast or irregular heartbeat
have stomach pain with nausea and vomiting o weight loss
Severe liver problems, including liver failure, can happen in people who take VIDEX. Your liver may become large (hepatomegaly), you may develop fat in your liver (steatosis), or you may have high blood pressure in the large vein of your liver (portal hypertension). Severe liver problems can lead to liver transplantation or death in some people taking VIDEX. Taking VIDEX with medicines that contain hydroxyurea or stavudine may increase your risk for liver problems.
You may be more likely to get lactic acidosis or severe liver problems if you are a female, are very overweight (obese), or have been taking nucleoside analogue medicines for a long time.
Call your healthcare provider right away if you have any of the following symptoms of severe liver problems:
yellowing of your skin or the white of your eyes (jaundice)
dark or "tea-colored" urine
light-colored stools (bowel movements)
pain, aching, or tenderness on the right side of your stomach area
For more information about side effects, see "What are the possible side effects of VIDEX?".
What is VIDEX?
VIDEX is a prescription medicine that is used with other antiretroviral medicines to treat Human Immunodeficiency Virus (HIV)-1 infection.
HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).
Do not take VIDEX if you take a medicine that contains:
Before you take VIDEX, tell your healthcare provider about all of your medical conditions, including if you:
have or had problems with your pancreas
have or had kidney problems
have or had liver problems, including hepatitis
have or had numbness, tingling, or pain in the hands or feet (peripheral neuropathy)
are receiving dialysis
are pregnant or plan to become pregnant. It is not known if VIDEX will harm your unborn baby.
Pregnancy Registry: There is a pregnancy registry for women who take antiretroviral medicines, including VIDEX during pregnancy. The purpose of the registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.
are breastfeeding or plan to breastfeed. Do not breastfeed if you take VIDEX.
You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.
It is not known if VIDEX can pass into your breast milk and if it could harm your baby.
Talk to your healthcare provider about the best way to feed your baby while taking VIDEX.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Some medicines interact with VIDEX Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
You can ask your healthcare provider or pharmacist for a list of medicines that interact with VIDEX.
Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take VIDEX with other medicines.
How should I take VIDEX?
Take VIDEX exactly as your healthcare provider tells you to take it.
Your healthcare provider will tell you how much VIDEX to take and when to take it.
Take VIDEX on an empty stomach at least 30 minutes before or 2 hours after you eat.
Your healthcare provider may change your dose if you have certain side effects. Do not change your dose of VIDEX without talking to your healthcare provider.
Shake the bottle well before taking each dose of VIDEX.
Be sure to close the bottle tightly after each use.
Do not miss a dose of VIDEX. If you miss a dose of VIDEX, take it as soon as possible.
It is important to take VIDEX on a regular schedule. The virus in your blood may increase and the virus may become harder to treat if you miss doses.
Your healthcare provider may lower your dose of VIDEX if your kidneys are not working well.
If you take too much VIDEX, go to the nearest emergency room right away.
What are the possible side effects of VIDEX?
See "What is the most important information I should know about VIDEX?"
Numbness, tingling, or pain in your hands or feet (peripheral neuropathy). Peripheral neuropathy is common during treatment with VIDEX and can be severe. Peripheral neuropathy happens more often in people who have advanced HIV-1 disease, have a history of peripheral neuropathy, or in people who are being treated with medicines that can cause neurologic problems.
Vision changes. Call your healthcare provider if you have changes in vision, such as blurred vision. You should have regular eye exams during treatment with VIDEX.
Changes in your immune system (immune reconstitution syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider if you start having any new symptoms after starting your HIV-1 medicine.
Loss of body fat (lipoatrophy) from the arms, legs, or face can happen during treatment with VIDEX. Your healthcare provider will monitor you for changes in your body fat. It is important to tell your healthcare provider if you notice any changes.
The most common side effects of VIDEX include:
stomach (abdomen) pain
These are not all the possible side effects of VIDEX.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store VIDEX?
Store VIDEX oral solution in a tightly closed container in the refrigerator between 36° F to 46° F (2° C to 8° C) for up to 30 days.
Safely throw away any unused VIDEX after 30 days.
Keep VIDEX and all medicines out of the reach of children.
General information about the safe and effective use of VIDEX
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use VIDEX for a condition for which it was not prescribed. Do not give VIDEX to other people, even if they have the same symptoms that you have. It may harm them.
You can ask your pharmacist or healthcare provider for information about VIDEX that is written for health professionals.
What are the ingredients in VIDEX?
Active ingredient: didanosine, USP
Inactive ingredients: Purified Water, USP and an antacid containing aluminum hydroxide (400 mg per 5 mL), magnesium hydroxide (400 mg per 5 mL), and simethicone (40 mg per 5 mL).
Resources for Staying Well
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Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Videx EC Drug Imprint
000876671_PB
capsule, white, imprinted with BMS 125 mg, 6671
capsule, white, imprinted with BMS 250MG, 6673
Didanosine 200 mg-BAR
capsule, green/white, imprinted with barr 200mg, 588
capsule, blue/white, imprinted with barr 250mg, 589
capsule, red/white, imprinted with barr 400mg, 590
Videx EC 250 mg


Home » How Does Europe's Foodservice Market Compare To The U.S.?
How Does Europe's Foodservice Market Compare To The U.S.?
We've known for a long time that the foodservice market in the Europe is significantly smaller than in the United States. New research from Peter Backman, principal at Horizons, the London-based research firm, details just how much smaller.
Backman toted up the populations and foodservice markets of the U.S. and the five largest sub-markets of the European markets. The combined populations of Germany, France, Spain, the United Kingdom and Italy are about equal to that of the U.S. But he calculates the foodservice market in the five countries is only 41% of the size of the market in the U.S. The big difference? What he calls the "popular" segments of the market: full-service and quick-service restaurants and drinking places. On the other hand, foodservice in hotels and in leisure operations is larger in Europe than in the U.S. Add together "popular" restaurants and lodging, and the combined market in the five European countries is still only 77% as large as in the U.S. He adds that the five account for about three-quarters of the total European foodservice market.
For information on Horizons research, go to hrzns.com.


One last Beignet and Cafe Au Lait before leaving New Orleans for Mississippi. We savored our last taste of N.O. at the big cafe situated right by Jackson Square, in the heart of the French Quarter called Cafe du Monde.
Statue of Andrew Jackson graces the center of the square.
If you read the history books they'll tell you that New Orleans was founded in 1718 by Jean-Baptiste Le Moyne de Bienville and that it was named for Philippe II, Duke of Orléans, who was Regent of France at the time. HOWEVER, the lesser told story is of the Portuguese explorer who actually stumbled into this area years before. Unfortunately, the explore was too intoxicated to know where he had landed, thus never having claimed the rights to the city. Years later Moyne de Bienville passed a law in his honor. The new law granted permission to all citizens, regardless of color, be allowed to be consume alcohol freely upon the streets of New Orleans. And so it was.
I was lucky to find this stature of the mysterious, drunkin' explorer titled "Capt'n Snagbird".
…we set out up the Muddy Mississippi, River Road through the Plantation-rich areas. Along the way we got to see river houses and people fishing along the banks.
It was a very nice drive through historic areas such as St. Francisville where we stopped for lunch at the Magnolia Cafe. We couldn't resist the Memphis BBQ sandwiches topped with slaw, that they had on special.
Mississippi was just a short distance from here, we passed into the state to find streets even more heavily lined with Spanish moss dripping trees and hand made signs declaring "Mud Bugs" on about every corner.
Vicksburg was on the map about halfway to Memphis so we decided to roll into town and just find any ol' place to lay our heads. Well, we were in for a surprise. This little town is full of excitement. It has lists of historical sights and museums, it sets right on the muddy Mississippi river, the citizens have put tremendous effort into attracting tourism with Riverboats converted to Casinos (it's legal to gamble here), parks, pretty streetlights and even their levee wall is painted by local artists depicting Vicksburg's history.
We drove right through main street and discovered a place called The Ware House Hotel. We stopped and inquired. It looked to rich for our taste but the location was great. It was 129.00 for a standard per night, so we said okay. Then after chatting with the owner it turns out that he is from San Diego (you can see the influence in the design here) and so he bumped us up to a suite room. Uhm, yes it's actually a loft style condo with all the amenities, even a view of the river!
After a few drinks at the hotel bar we became friends with the bartender Laytoya and soon decided we'd start the new Jackson Three. Janet (me), Laytoya and Michael (played by Dennis of course)…she was really a hoot. She and Dennis decided to have a "worm" contest that never did pan out. Oh well, she did recommend a restaurant to us called "Rusty's" though, that did pan out!
We walked down the main street, which was lined with some very new looking shops and some completely empty, old, buildings as well. The town was quiet and seemed on the surface, almost vacant at about five in the afternoon.
As though we were the only people in town, we frolicked about the streets and discovered a playground near the water.
We got to Rusty's and as soon as we opened the door… we figured out where all the towns people were. They were at Rusty's… no doubt.
Dennis had Filet Mignon with a baked sweet potato and I had the Red Fish with Crawfish sauce and cheese grits. For dessert we couldn't resist the Mississippi Mud Pie!
« Day 16 – Local Flavor, on the Side!
that condo, hotel, loft , is just what you need in s.d. i love it.
looks just like your style too.


text:
Dave Rubin is a classical liberal comedian and commentator. He's also the host of the fan-funded YouTube talk show, the Rubin Report.
Free Speech, Muhammad Cartoons, and Islamism in Europe: Dave Rubin's Interview with Flemming Rose
"I didn't choose this fight. It was imposed upon me eleven years ago, when I was the editor responsible for publication of the so-called Danish Muhammad cartoons. "
Dave Rubin and Deirdre McCloskey: Free Trade, Trans in Academia, and the (Classical) Liberal Heritage — Full Interview
One of the things that I've really been making the focus of this show is to show people what real, true, classical liberalism is.
Education, Free Speech, and Elite "Temper Tantrums": Interview with Dave Rubin and Joanna Williams
2 years ago	Education
"One of the big problems at the moment with education is that the role of the teacher has become so confused with the role of the parents."
Why it's so hard for government to fix social problems
2 years ago	02:42
What if the government can't solve our problems because the government doesn't really exist? Prof. Mike Munger explains his "unicorn" theory of the state.
An Alternative to Welfare
Today's welfare system discourages aspiring for the American dream. What if we tried a universal basic income instead? Watch the full interview with Prof. Munger
An Academic Case for Safe Spaces
Prof. Mike Munger supports safe spaces on campus — but no one should be "safe" from hearing ideas they disagree with across the whole school.
The Unprecedented Equality of the 21st Century
The rich get richer, and the poor get … cell phones, cars, and nice TVs? Prof. Mike Munger says we're actually more equal than ever. Click to watch the full interview.
The History of Police Militarization
Why did the police start using militarized tactics and equipment on American citizens? Dr. Abby Hall says the line between law enforcement and war is getting dangerously blurry.
When Foreign Policy Comes Home: The Boomerang Effect
The skills and technologies the US government develops to control foreign populations can boomerang back and be used against Americans. For the full interview click here.
An Economist Explains Foreign Policy
Can economics tell us what kind of foreign policy will work in Syria or around the world?
The Big Tent of Liberalism
From the beginning, classical liberalism has been a big tent with a wide diversity of ideas inside it. Watch the full interview with Dave Rubin and Brandon Turner here .
Tocqueville's Fear With Democracy: Soft Despotism
Alexis de Tocqueville feared that Americans would willingly give up freedom for a "soft despotism." Full interview here.
Why You Should Tolerate Wrong Opinions
Real tolerance means accepting free speech even for people whose opinions are 100% wrong. Full interview with Dave Rubin and philosopher Brandon Turner here: https://www.youtube.com/watch?v=VFrLpk5OXfU

redpajama_set_name: RedPajamaCommonCrawl


Jackson, Andrew; Lampkin, Nicolas and Fowler, Sue (2004) Organic farm incomes in England and Wales 1999/00 and 2000/01. University of Wales Aberystwyth , Institute of Rural Sciences.
This report presents results from research work carried out for the Department for Environment, Food and Rural Affairs (DEFRA) on the financial performance of organic farms for 1999/00 and 2000/01 financial years. The aim of the report is to collate financial data for organic farms differentiated by farm type, in order to provide continuity between previous studies (project code: OF 0190) on the economics of organic farming covering years 1995/96 to 1998/99 and new research work carried out by the Institute of Rural Sciences, UWA, to obtain financial information for organic farms for the period 2001/02 to 2003/04 (project code: OF 0189).
The financial data in this report were not collected directly, but were derived from other DEFRA-funded studies. Data are from farms of varied sizes within the samples for each farm type and not always of adequate sample size. This was particularly the case for horticulture while other datasets mainly comprised five farms or more per farm type. A cautious approach is required when viewing smaller farm samples as it is not possible to draw conclusions on the organic sector from these results; but may permit observation of data trends for the particular set of farms within the sample. Where possible, to provide an idea of economic trends over time, continuous farm data for 1998/99 and in some cases for 2001/02 are shown alongside the 1999/00 and 2000/01 data.
The report highlights results for organic cropping, horticulture, dairy, lowland and LFA cattle and sheep farms and one set of results for in-conversion dairy farms. Comparable conventional farm datasets are shown alongside some organic datasets for comparison. This was the case for both organic and in-conversion dairy farms and LFA and lowland cattle and sheep farms for 2000/01 datasets only.
From this report, the financial data show that most farm types under organic management had positive net farm incomes (NFI) with the exception of the in-conversion dairy farm sample. Management and investment incomes (MII) were positive values for all farm types with the exception of lowland and LFA cattle and sheep farms from the FBS sample. The financial trends varied by farm type between 1999/00 and 2000/01 with the organic cropping farm sample experiencing over 60% reduction in NFI, whilst organic dairy and LFA cattle and sheep farm incomes increased at varying levels over the two years. For all farm types where comparable data are shown alongside the organic farm sample, the organic sample showed higher NFI and MII values with the exception of the in-conversion dairy farm sample where income values were lower than the comparable dataset.
Gross margin data are presented for organic dairy herds, LFA suckler cows and finished beef stock and LFA breeding ewe flocks. Arable gross margins are shown for winter wheat, spring wheat, oats, beans and potatoes crops and horticultural data are available for potatoes, carrots, beetroot and calabrese.


The CAST CTRPC Remote Photo Cell attaches to the transformer to switch on power at dusk. This is typically used in conjunction with a CAST Timer. The remote unit is equipped with a 15' lead wire to allow for remote positioning of the photocell.
The CAST Remote Photo Cell attaches to the transformer to switch on power at dusk.


text:
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The Morocan Dirham
The dirham is the legal tender in Morocco, made up of 100 units each of them called a santim. Dirhams are the official Moroccan currency since 1882, and they come in coins of nine denominations and banknotes of four denominations.
Before 1882, when the new monetary system was introduced, Morocco issued copper coins called falus, silver dirhams and golden benduqui. In 1882, the dirham became a multiple of the rial coins.
In 1960, after the end of the French protectorate, the country introduced the dirham again to replace francs (1 dirham equalled 100 francs). This currency still circulated until 1974.
Current Moroccan dirham banknotes
The first dirham banknotes were overprints on earlier franc banknotes, in denominations of 50 dirhams (on older 5,000 franc notes) and 100 dirhams (on 10,000 franc notes). In 1965 new notes were issued for 5, 10 and 50 dirhams. 100 dirham notes were introduced in 1970, followed by 200 dirham notes in 1991 and 20 dirham notes in 1996. 5 dirham notes were replaced by coins in 1980 and 10 dirham notes were replaced by coins in 1995.
The current series of banknotes, , issued in the reign of Mohammed VI, circulates together with the series issued in the reign of his father, King Hassan II. Both series circulate together normally, but the notes issued under the former monarch are being gradually replaced by the new ones. The colours for both series are the same, unchanged, only the design of the new series varies with the effigy of the new monarch and its more modern graphic design and newer security measures.
Nowadays there are 20, 50, 100 and 200 dirham notes in circulation. For more information check Bank Al-Maghrib's web page, which issues the banknotes and coins for this currency.
Current dirham coins in use
In 1960 new 1 dirham coins were issued in silver, and for 1 and 5 dirham coins, in nickel in 1965. In 1974 a new monetary system started with the issuing of centimes, in denominations of 1, 5, 10, 20 and 50 centime coins and 1 dirham coins. 1 centime coins were minted in aluminium, 5, 10 and 20 centime coins in bronze-aluminium and the rest in cupro-nickel. In 1980 a new coin of 5 dirhams was issued, but was soon replaced by a bimetallic coin of the same value in 1987. In 1995 a new bimetallic 10 dirham coin was added.
The current legal tender coins were issued in the year 2002, and they gradually replaced the former series bearing the bust of King Hassan II. These 5 and 10 dirham coins are bimetallic and 1 centime coins are no longer minted, although they were never officially removed from circulation. In 2002 a new 2 dirham denomination was introduced.
The coins currently in circulation are 5, 10 and 20 centime coins, and 0.5, 1, 2, 5 and 10 dirhams. Check Bank Al-Maghrib's web page for more information. .
Interesting facts of the Moroccan dirham
The plural for dirham is darahim, although in English and French the word dirhams is commonly used.
The centimes of dirhams are called francs or santimat.
One dirham is divided into 100 francs or santimat.
In countryside markets the reales (rial) and duros (doro) are still used.
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text:
Q: Formatação para dispositivos moveis Eu posso usar @media screen and (orientation:portrait) {} para que meu código funcione apenas em dispositivos moveis ?
Pois creio que celulares e smartphones são os únicos que possuem $(window).height() maior que $(window).width() ou a altura da tela maior que a largura.

A: Não, porque smartphones e tablets ficam em landscape quando girados. Por isso é bom especificar também os limites em "px".
Neste link tem media queries padrões para os dispositivos. Mas cada layout é um layout, portanto se baseia nesse padrão mas testa os breakpoints da página e edita as media queries como for preciso.
Podes fazer manualmente, diminuindo o tamanho da janela do navegador, usando extensões (eu uso essa no Chrome) ou sites como esse.

redpajama_set_name: RedPajamaStackExchange


text:
Михаил Александрович Авилов (21 ноября 1907, станица Цимлянская — июнь 1974) — русский советский поэт.

Жизнь и творчество
Родился Михаил Александрович Авилов 21 ноября 1907 года на Дону, в станице Цимлянской в казачьей семье лейб-лекаря. Его отец был фельдшером и ветеринаром и обучал Михаила верховой езде. С детства мальчик любил и понимал лошадей, это и определило его будущую профессию.

М. А. Авилов — поэт нелегкой судьбы. Любовь к поэзии проявилась у него ещё в то время, когда он учился в трудовой школе: любил читать стихи, учил их наизусть. Первое его стихотворение появилось в школьной газете.

Михаил Александрович Авилов стихи писал всегда, когда работал грузчиком в Новочеркасске, помощником врубмашиниста на Луганщине, когда по окончании Новочеркасского зооветеринарного института в 1931 году стал сельским ветврачом, когда был в плену.

В предисловии к своей книге стихов «Бессмертник» М. Авилов так пишет о своей нелегкой судьбе:

Вера в человека советской закалки, способного вынести адские муки и устоять, любящего жизнь и ненавидящего фашизм, — такова главная тема творчества поэта Михаила Авилова. Она развивается в сборнике «Бессмертник», вышедшем в Ростовском издательстве в 1961 году. Цикл стихов «За колючей проволокой» — свидетельство бесстрашия советского человека, его мужества, преданности Родине. Она звучит и во втором сборнике «С именем человека» (Ростиздат, 1963), в котором входят поэмы «Дон-Кихот» и «Сказка о богатырях и спящей царевне».

Сильным, мужественным людям посвятил М. Авилов и поэму «Цвет времени» — о комсомольской молодежи 20-х годов, самоотверженно трудившейся на полях Придонья под пулями кулацких обрезов.

Последнее произведение М. А. Авилова — поэма «Пепел» (Ростиздат, 1970) — также о несгибаемой духовной силе советского человека, о гордых борцах, сильных высокой гражданской и нравственной идеей, борющихся против фашизма.

Произведения
 Авилов, М. А. Бессмертник: Стихи. — Р/Д: Кн. изд-во, 1961. — 56 с., портр.
 Циклы: За колючей проволокой; После грозы.
 Авилов, М. А. С именем человека: Поэмы. — Р/Д: Кн. изд-во, 1963. — 27 с.
 Содерж.: Дон-Кихот; Сказка о богатырях и спящей царевне.
 Авилов, М. А. Пепел: Поэма. — Р/Д: Кн. изд-во, 1967. — 22 с., портр.
 переиздание — Р/Д: Кн. изд-во, 1970. — 48 с., ил.
 Авилов, М. А. Цвет памяти: Стихи и поэмы — Р/Д: Кн. изд-во, 1977. — 79 с., ил. 1 л. портр.
 Циклы: Бессмертник; Разговор с современником; После грозы; Из последних стихов; Поэмы: Пепел; Цвет времени; Неоконченная поэма.
 Авилов, М. А. Бессмертник: Стихи и поэмы — Р/Д: Кн. изд-во, 1982. — 63 с.
 Содерж.: Стихи; Цвет времени: Поэма; Пепел: Из поэмы.

Публикации в коллективных сборниках и журналах (стихи)
 «Из последних тетрадей»: «Стою у моря на обрыве…»; «Романтики, собратья Робинзона…»; «Но после нас живущим нужно знать…»; «Пустая ссора…» // Дон. 1977 — № 12 — С. 107—109.
 «В ночь на 10 мая 1945 года»; Советским солдатам; «Я шел смоленскими полями…»; «Я вижу в степи и далекое стадо…» — В кн.: От Дона до Победы. Р/Д, 1985, с. 5—7.

О жизни и творчестве М. А. Авилова
 Долинский Д. Маленькие открытия // Комсомолец. — 1959. — 30 декабря
 Анисимов Л. Заявка на зрелость // Молот. — 1960 — 8 июня
 Котовсков В. Дорогой мужества // Молот. — 1965 — 18 февраля
 Котовсков В. Поэт мужественного сердца // Молот. — 1967 — 21 ноября
 Ефремов В. «Стремление к справедливости при любых обстоятельствах…» // Комсомолец. — 1974 — 14 сентября
 Бугаенко Н. Стихи о мужестве // Веч. Ростов. — 1983. — 12 марта
 Гегузин И. Поэт мужества: [о сб. «Цвет памяти» М. Авилова] // Лит. Россия. — 1977. — 25 февраля. — С. 20
 Долинский Д. О поэме «Пепел» М. Авилова // Дон. — 1971. — № 12. — С. 177
 Ефремов В. О сборнике «Цвет памяти» М. Авилова // Лит. обозрение. — 1977. — № 10. — С. 40—41
 Моложавенко В. Пролог: [о поэте М. Авилове] // В кн. В. С. Моложавенко Костры памяти. — Р/Д: Кн. изд-во, 1985. — С. 9
 Моложавенко В. За нами — Москва: [о М. Авилове] // В кн. В. С. Моложавенко Костры памяти. — Р/Д: Кн. изд-во, 1985. — С. 163—165
 Рогачев А. О сборнике «Цвет памяти» М. Авилова // Дон. — 1977. — № 6. — С. 180
 Русиневич К. Торжество жизни: [о сб. «Бессмертник» и поэме «Пепел» М. Авилова] // Молот. — 1971. — 20 июня
 Скребов Н. «Создать, открыть и покорить» // Дон. — 1974. — № 11. — С. 67—68
 Скребов Н. Возвел он песню в звание солдата // Молот. — 1977. — 22 ноября
 Чекалин С. Мужество: [о сб. «Бессмертник» М. Авилова] // Комсомолец. — 1984. — 14 февраля

Примечания

Литература
 Писатели Дона: Библиографический указатель. — Изд. 2-е, испр. и доп. — Ростов н/Д: Кн. изд-во, 1986. — 416 с.

Ссылки
 Авилов Михаил Александрович
 Праведник, вернувшийся из ада
 Авилов Михаил Александрович (1907—1974)

Персоналии:Ростовская область

redpajama_set_name: RedPajamaWikipedia


Award-winning Chef Chad Gauss and his team bring The Food Market's flair for fun and dining excellence straight from the chef to your table, no matter where the table is.
Eleven Courses is recognized as an industry trendsetter with an unwavering commitment for bringing cEATivity and innovation to every event.
Andy Nelson's Barbecue Catering has been providing the best food and BBQ for Maryland for over 30 years.


Department of Mechanical Engineering and Center for Bioengineering, University of Washington, Seattle, Wash.
The use of Doppler ultrasonics provides one of the few, if not the only, methods of noninvasive measurement of blood flow and velocity in the body. In terms of overall accuracy the pulsed ultrasonic Doppler flow meter, operating in a radar-like range-gated manner, currently offers the best solution. However, under certain circumstances this device suffers from an inherent lack of spatial resolution, resulting in the distortion of the measured velocity profiles. The device is modeled as a convolution integral, incorporating the physical characteristics of the flow meter, and those of the velocity field, as established in previous work. The distortion of the measured velocity profile is corrected by solving the integral equation, or "deconvolving" using the discrete Fourier transforms implemented on a digital computer. The methods discussed for obtaining the "true" velocity profile require only a knowledge of the flow meter characteristics and its output. No assumptions as to the nature of the true profile are necessary.
Jorgensen JE, Garbini JL. An Analytical Procedure of Calibration for the Pulsed Ultrasonic Doppler Flow Meter. ASME. J. Fluids Eng. 1974;96(2):158-167. doi:10.1115/1.3447122.


Which configurations are at risk?
Why is this a high risk vulnerability?
The vulnerability is in DirectShow's code to process QuickTime format. The QuickTime Movie Parser Filter in DirectShow has been removed from Windows Vista and later operating systems (see http://msdn.microsoft.com/en-us/library/dd377491(VS.85).aspx). Windows Vista, Window Server 2008, and later versions of Windows are not affected by this vulnerability. Older Windows platforms are vulnerable, as shown in the advisory.
If I have installed Apple's QuickTime, am I safe?
Our investigation has found that the installation of Apple's QuickTime does NOT mitigate this DirectShow's vulnerability.
To be clear, whether you've installed Apple's QuickTime or not, the vulnerability is in the Microsoft's quartz.dll and it's possible to craft an attack to call that DLL on the system regardless of whether Apple's QuickTime is present.
The vulnerability is in the DirectShow platform (quartz.dll). While the vulnerability is NOT in IE or other browsers, a browse-and-get-owned attack vector does exist here via the media playback plug-ins of browsers. The attacker could construct a malicious webpage which uses the media playback plug-ins to playback a malicious QuickTime file to reach the vulnerability in Quartz.dll. Please note this type of attack could happen for any browsers, not IE specific.
There is also a file-based attack vector by opening a malicious QuickTime file via Windows Media Player to trigger the vulnerability.
There are several workarounds that you may consider here.
This is the best workaround because it's the most surgical. It only disables QuickTime Parsing in DirectShow. DirectShow's other functionality is not affected. This workaround covers all known attack vectors. Therefore, if you are not concerned about QuickTime content playback via DirectShow, this is the workaround we recommend you apply.
The advantage of this workaround is that it still allows you to use Windows Media Player (or other applications) to playback QuickTime content via DirectShow. The disadvantage is that it only protects against the current attacks we see that use IE. Other attack vectors are not covered. For example, it won't protect other browsers.
This workaround is effective but can have significant impacts in your environment. Please refer to our previous SRD blog: "MS08-033: So what breaks when you ACL quartz.dll?" to get more details on this.
We don't recommend this workaround because #1 provides the same level of protection with less impact. However, it is an option listed in the advisory because it is effective protection and to give customers as full a range of options as possible to better protect their environment.


The Beach House is a great choice if you want a quiet vacation surrounded by natural beauty. You'll be stunned by the sea view, and can enjoy it from several spots on the deck and balcony. You can swim laps in the infinity pool, soak in the plunge pool, and sunbathe all over the property. Everyone will have plenty of space, since the bedrooms are spread out on different sides of the villa. This villa would be great for a couples' getaway with friends.
The Beach House is a three-bedroom oceanfront villa on Crescent Beach, Bequia. This property offers peaceful privacy, ocean views, and indoor/outdoor living and dining.
The villa's elevated position overlooking Crescent Beach guarantees stunning beach views. Mature coconut palms stretch down to Bequia's turquoise waves, and the entire bay is in clear view from the multi-leveled terrace. There's several spaces to lounge and dine in the shade and in the sunshine. Some terraces are oceanfront, and some are in the garden courtyard at the center of the property. There's also a lap pool, a plunge pool, and a gas BBQ grill; and every level connects via a winding staircase. Lush, manicured gardens contrast the sleek architectural lines.
Most of the buildings have an open-air design, with wide French doors that can be opened or closed to the island breezes. The wood floors are highly polished, and the interiors combine classic colonial charm with chic accents. The kitchen's turquoise backsplash mimics the sea and is fully equipped with stainless steel appliances, a gas stove, and a coffeemaker. At the sister property, Beach Villa, there is a small laundry room with a washer and tumble dryer. Daily maid service is also included. On the Beach House's upper level, there's a double suite overlooking the pool, terraces, and Crescent Bay. This suite has a private bathroom with a walk-in shower. The lower level features two identical double suites that also have private bathrooms with walk-in showers. All three bedrooms have exterior access, wardrobes, and French doors.
The Beach House is a private, intimate getaway with views of the island's rugged beauty. There's some local restaurants within a 10-15 minute drive, but this villa's greatest feature is its seclusion.
2 pools. One is located on the upper level and the other is located on the lower level.
We enjoyed our stay at The Beach House. It is on the quieter side of the island overlooking Crescent Beach. We rented a car, and Port Elizabeth is a 10-15 minute drive. In our opinion, it would be very difficult to walk back and forth to town or the Caribbean beaches from this location. The house itself is very nice and built for privacy. There are five pods, three with bedrooms and baths, one containing the kitchen, and one containing the living room. This rental does not have any TVs, but does offer Wi-Fi. The pool upstairs is small, but nice for taking a dip after coming back from the beach. The pool on the lower level is even smaller, and we did not use it. Overall, we enjoyed our stay at The Beach House and the property manager Jerry was very helpful.
Shawna was great to work with.


I think this story resonates with me because I see myself in the young man in the story. I made some similar statements when I finished my studies at the seminary. I remember being sure that I never wanted to study canon law and I never wanted to return to the seminary. But God saw something different in me and I was sent to Rome to study canon law. When I returned from my studies, I was made rector of the same seminary I never wanted to return to. I never could have imagined those turns in my life. God gave me everything I did not want and erased any story I could have imagined.
I suppose it is often true that when left to our own devices and reasoning, we often make small, superficial and self-serving choices in life. In the end what saves us from a self-serving, small, uninspired life is love. But not any kind of love, it is the transforming sacrificial love revealed by the Word Made Flesh, Jesus Christ on the cross. On the cross Jesus sacrificed His life for us so we can have life more abundantly.
This kind of love seems too impossible to bear or is made to seem ridiculous in the secular culture that surrounds us. We often run from it like the young man in the commercial, but love captures us unexpectedly and sacrificial love peels away our self-centeredness and opens us to the joy of love. Thank goodness we don't have to make big sacrifices at the beginning, because we are kind of tricked by falling in love, or blessed with joyful graces that make us feel in control at the beginning. But eventually the demands of love strip away anything that keeps us from deepening our commitment. Just when we feel we have nothing to give, we find a new strength. It feels like we are giving up everything, but we are just making room for something better.
Jesus this Holy Week embraces his cross. He knows it will be hard and in the garden of Gethsemane he begs his Father, "Let this cup pass away from me" but in the end Jesus remains faithful to the demands of love, the will of his Father. This is our life at times, the demands of love invite us deeper into the mystery of love and it costs us dearly. Caring for parents that need more help, for the needs of an ill child or spouse, volunteering to help a neighbor or relative, trying to heal strife in a family or rekindle love all take time and effort and will demand that we let something else go to embrace these demands of love. Like Jesus on the Cross, it feels like dying, in fact, it is a dying to self. But Jesus who died on the cross did not remain in the tomb, but was resurrected to new life. So too if we die with Christ in remaining faithful to our commitments of love, we resurrect with a new heart now free to love with a depth we never expected and we are connected to others with a love so deep it is frightening and wonderful at the same time.
In the short commercial I mentioned above, the young man takes this journey of love. I have found this journey of love in my priesthood and as your bishop. I pray that this Holy Week and Easter will be filled with a grace to help us all to cast off our self-centeredness and sin and embrace the demands of love. It will feel like dying, but it is really the path of new life and resurrection.


Bulbine: One of my favorite border plants!
Bulbine frutescens is a species of flowering plant in the genus Bulbine. Its common names are Yellow bulbine, Snake flower, Cat's tail, Burn jelly plant.
It is one of my favorite plants to use as a border in a high traffic sunny spot and gardens where children play. It is originally from South Africa and doesn't mind our hot Houston summers and did just fine through are cold weather with temps dipping down to 18 degrees. The word Bulbine comes from the Latin word bulbus; meaning bulb, onion or edible bulb. This is misleading because the plants don't have a bulbous base. It is a clumping form evergreen perennial succulent with long narrow juicy leaves. It stays about 18 inches high and spreads up to 2 feet. Bulbine thrives in full sun to light shade. The flowers come in orange and yellow blooming on tall spike or stalk that dance above the foliage. It is suited for gardens in USDA Zones 9-11.
Bee on bulbine in our holding area.
Bulbine is great for attracting bees, butterflies and birds. It is very drought tolerant and suitable for xeriscaping. It does want regular water but doesn't like to be over watered. And it also does just fine in a container.
Bulbines soft juicy leaves won't bother walkers when they brush up against them.
They have long juicy leaves. And the juice of the leaves, much like aloe, is said to help sooth rashes, scrapes, insect bites burns, blisters, cracked lips and areas of cracked skin. This makes it a great little first-aid plant. In my research I found that in its native habitat the indigenous people make an infusion of a few fresh leaves by boiling it with water. They strained drink is taken for coughs, colds and arthritis.
I grow Bulbine and I love it but I had no idea that you could get it in orange. I shall look out for this one. How pretty.
Bulbine is a terrific plant. I grow it in my zone 8 garden, which means some winters I lose it. There was a long span where our winters were so mild, my clumps grew like crazy. When that happens, it's easy to divide the clumps and spread them around.
Hi Ally, it is said to be able to handle 20 degrees but it is really a heat loving plant. I do love how easy it is and how long it flowers. I just started using the orange and mixing it in with the yellow.