Videx

Didanosine is an oral medication that is used for the treatment of infections with the human immunodeficiency virus (HIV). It is in a class of drugs called reverse transcriptase inhibitors which also includes zalcitabine (Hivid), zidovudine (Retrovir), stavudine (Zerit), and lamivudine (Epivir). During infection with HIV, the HIV virus multiplies within the body's cells. The newly-formed viruses then are released from the cells and spread throughout the body where they infect other cells. In this manner, the infection spreads to new, uninfected cells that the body is continually producing, and HIV infection is perpetuated. When producing new viruses, the HIV virus must manufacture new DNA for each virus. Reverse transcriptase is the enzyme that the virus uses to form this new DNA. Specifically, didanosine is converted within the body to its active form (dideoxyadenosine triphosphate). This active form is similar to a chemical, deoxyadenosine triphosphate, that is required by the HIV virus to make new DNA. The reverse transcriptase uses dideoxyadenosine triphosphate instead of deoxyadenosine triphosphate for making DNA, and the dideoxyadenosine triphosphate that interferes with the reverse transcriptase. Didanosine does not kill existing HIV virus and it is not a cure for HIV. The FDA approved didanosine in October 1991.

Adults weighing 60 kg or more should receive 400 mg once daily of the capsules or 200 mg twice daily of the powder. Adults weighing less than 60 kg require 250 mg once daily of the capsules and 125 mg twice daily of the powder.

Didanosine should be administered on an empty stomach because food reduces the absorption of didanosine by as much as 46%.

Videx is part of the drug class:

• Nucleoside and nucleotide reverse transcriptase inhibitors

Before you take Videx, tell your healthcare provider if you:

• have or had kidney problems
• have or had liver problems (such as hepatitis)
• have or had persistent numbness, tingling, or pain in the hands or feet (neuropathy)
• have any other medical conditions
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed

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

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Videx (didanosine oral solution):

• For adults who weigh at least 60 kg (132 lbs.) the recommended dosage is 200 mg twice daily OR 400 mg once daily.
• For adults who weigh less than 60 kg (132 lbs.) the recommended dosage is 125 mg twice daily OR 250 mg once daily.
• For children (2 weeks old to 18 years old)
  • Between 2 weeks and 8 months old, the recommended dosing is 100 mg/m2 twice daily.
  • For those greater than 8 months old, the recommended dosing is 120 mg/m2 twice daily but not to exceed the adult dose.

Didanosine is used in combination with other medicines for the treatment of human immunodeficiency virus (HIV) infection. HIV is the virus that causes acquired immune deficiency syndrome (AIDS).

Didanosine will not cure or prevent HIV infection or AIDS. It helps keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay the development of problems usually related to AIDS or HIV disease. Didanosine will not keep you from spreading HIV to other people. People who receive this medicine may continue to have the problems usually related to AIDS or HIV disease.

This medicine is available only with your doctor's prescription.

The buffered tablets that are to be chewed, crushed or mixed with water are no longer available in the United States. This product was voluntarily discontinued, and it was not due to safety concerns. Didanosine delayed-release capsules (Videx® EC) and pediatric powder for oral solution are still available.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of too much lactic acid in the blood (lactic acidosis) like fast breathing, fast heartbeat, a heartbeat that does not feel normal, very bad upset stomach or throwing up, feeling very sleepy, shortness of breath, feeling very tired or weak, very bad dizziness, feeling cold, or muscle pain or cramps.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Swelling of belly.
• Very bad dizziness or passing out.
• A burning, numbness, or tingling feeling that is not normal.
• Any unexplained bruising or bleeding.
• Change in eyesight.
• Change in body fat.
• This medicine may help the immune system work. If you have an infection that you did not know you had, it may show up when you take Videx. Tell your doctor right away if you notice any signs of infection like fever, sore throat, weakness, cough, or shortness of breath after you start this medicine.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Belly pain.
• Upset stomach or throwing up.
• Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Videx is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Videx or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Videx. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

The following serious adverse reactions are described below and elsewhere in the labeling:

• Pancreatitis [see Boxed Warning, Warnings and Precautions (5.1)] • Lactic acidosis/severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.2)] • Hepatic toxicity [see Warnings and Precautions (5.3)] • Non-cirrhotic portal hypertension [see Warnings and Precautions (5.4)] • Peripheral neuropathy [see Warnings and Precautions (5.5)] • Retinal changes and optic neuritis [see Warnings and Precautions (5.6)]

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.

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

	Percent of Patients*
	ACTG 116A		ACTG 116B/117
Adverse Reactions	Videx n=197	zidovudine n=212	Videx n=298	zidovudine n=304
*  The incidences reported included all severity grades and all reactions regardless of causality.
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

Table 4:      Selected Clinical Adverse Reactions from Combination Studies

	Percent of Patientsa,c
	AI454-148b		START 2b
Adverse Reactions	Videx + stavudine + nelfinavir n=482	zidovudine + lamivudine + nelfinavir n=248	Videx + stavudine + indinavir n=102	zidovudine + lamivudine + indinavir n=103
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.
Diarrhea	70	60	45	39
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	*

Pancreatitis resulting in death was observed in one patient who received Videx (didanosine) plus stavudine plus nelfinavir in Study Al454-148 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 (5)].

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

	Percent of Patients
	ACTG 116A		ACTG 116B/117
Parameter	Videx n=197	zidovudine n=212	Videx n=298	zidovudine n=304
ULN = upper limit of normal.
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

Table 6:      Selected Laboratory Abnormalities from Combination Studies (Grades 3-4)

	Percent of Patientsa
	AI454-148b		START 2b
Parameter	Videx + stavudine + nelfinavir n=482	zidovudine + lamivudine + nelfinavir n=248	Videx + stavudine + indinavir n=102	zidovudine + lamivudine + indinavir n=103
ULN = upper limit of normal. NC = Not Collected. a  Percentages based on treated subjects. b  Median duration of treatment 48 weeks.
Bilirubin (greater than 2.6 x ULN)	less than 1	less than 1	16	8
SGOT (AST) (greater than 5 x ULN)	3	2	7	7
SGPT (ALT) (greater than 5 x ULN)	3	3	8	5
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

Table 7:      Selected Laboratory Abnormalities from Combination Studies (All Grades)

	Percent of Patientsa
	AI454-148b		START 2b
Parameter	Videx + stavudine + nelfinavir n=482	zidovudine + lamivudine + nelfinavir n=248	Videx + stavudine + indinavir n=102	zidovudine + lamivudine + indinavir n=103
NC = Not Collected. a  Percentages based on treated subjects. b  Median duration of treatment 48 weeks.
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

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 (14)].

Retinal changes and optic neuritis have been reported in pediatric patients.

Postmarketing Experience

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, and redistribution/accumulation of body fat [see Warnings and Precautions (5.8)].   Digestive Disorders – anorexia, dyspepsia, and flatulence.   Exocrine Gland Disorders – pancreatitis (including fatal cases) [see Boxed Warning, Warnings and Precautions (5.1)], sialadenitis, parotid gland enlargement, dry mouth, and dry eyes.   Hepatobiliary Disorders – symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis [see Boxed Warning, Warnings and Precautions (5.2)]; non-cirrhotic portal hypertension [see Warnings and Precautions (5.4)]; 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 (5.6)]. Use with Stavudine- and Hydroxyurea-Based Regimens

When didanosine is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when didanosine is used alone. Thus, patients treated with Videx in combination with stavudine, with or without hydroxyurea, may be at increased risk for pancreatitis and hepatotoxicity, which may be fatal, and severe peripheral neuropathy [see Warnings and Precautions (5)]. The combination of Videx and hydroxyurea, with or without stavudine, should be avoided.

Pregnancy

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 (5.2)]. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk. Healthcare providers caring for HIV-infected 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.

Nursing Mothers

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.

Pediatric Use

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 (2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14)].

Geriatric Use

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 (5.1)]. 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 (2.2)].

Renal Impairment

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 (12.3)]. A dose reduction is recommended for these patients [see Dosage and Administration (2)].

Mechanism of Action

Didanosine is an antiviral agent [see Microbiology (12.4)].

Pharmacokinetics

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

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.
			Pediatric Patientsb
Parameter	Adult Patientsa	n	8 months to 19 years	n	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

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 (2)]. Videx should be taken on an empty stomach.

Special Populations

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 (2.2).]

Table 11:      Mean ± SD Pharmacokinetic Parameters for Didanosine Following a Single Oral Dose

	Creatinine Clearance (mL/min)
Parameter	at least 90 n=12	60-90 n=6	30-59 n=6	10-29 n=3	Dialysis Patients n=11
ND = not determined due to anuria. CLcr = creatinine clearance. CL/F = apparent oral clearance. CLR = renal clearance.
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

Hepatic Impairment: The pharmacokinetics of didanosine have been studied in 12 non-HIV-infected 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 (2.3).]

Pediatric Patients: 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 (14.2) and Use in Specific Populations (8.4).

Geriatric Patients: Didanosine pharmacokinetics have not been studied in patients over 65 years of age [see Use in Specific Populations (8.5)].

Gender: The effects of gender on didanosine pharmacokinetics have not been studied.

Drug Interactions

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 (2.3 for Concomitant Therapy with Tenofovir Disoproxil Fumarate), Contraindications (4), and Drug Interactions (7.1 and 7.2).

Table 12:      Results of Drug Interaction Studies with Videx: Effects of Coadministered Drug on Didanosine Plasma AUC and Cmax Values

			% Change of Didanosine Pharmacokinetic Parametersa
Drug	Didanosine Dosage	n	AUC of Didanosine (95% CI)	Cmax of Didanosine (95% CI)
↑  Indicates increase. ↓  Indicates decrease. ↔  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.
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	↔	↔

Table 13:      Results of Drug Interaction Studies with Videx: Effects of Didanosine on Coadministered Drug Plasma AUC and Cmax Values

			% Change of Coadministered Drug Pharmacokinetic Parametersa
Drug	Didanosine Dosage	n	AUC of Coadministered Drug (95% CI)	Cmax of Coadministered Drug (95% CI)
↑  Indicates increase. ↓  Indicates decrease. ↔  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  Tenofovir disoproxil fumarate. d  Patients less than 60 kg with creatinine clearance of at least 60 mL/min. NA = Not available.
ciprofloxacin, 750 mg every 12 hours for 3 days, 2 hours before didanosine	200 mg every 12 hours for 3 days	8b	↓ 26%	↓ 16%
750 mg single dose	buffered placebo tablet	12	↓ 98%	↓ 93%
delavirdine, 400 mg single dose simultaneous 1 hour before didanosine	125 mg or 200 mg every 12 hours 125 mg or 200 mg every 12 hours	12b 12b	↓ 32% ↑ 20%	↓ 53% ↑ 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 daily1 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%)

Microbiology

Mechanism of Action

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.

Resistance

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 didanosine-treated patients showed mutations in the reverse transcriptase gene that resulted in the amino acid substitutions K65R, L74V, and M184V. 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, zalcitabine, and zidovudine in cell culture. These isolates harbored five substitutions (A62V, V75I, F77L, F116Y, and Q151M) in the reverse transcriptase gene. In data from clinical studies, the presence of thymidine analogue mutations (M41L, D67N, L210W, T215Y, K219Q) has been shown to decrease the response to didanosine.

Read this Medication Guide before you start taking Videx and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment. You should stay under your healthcare provider’s care when taking Videx.

What is the most important information I should know about Videx?

Videx may cause serious side effects, including:

1. Swelling of your pancreas (pancreatitis) that may cause death. Pancreatitis can happen in people: • who take Videx by itself, and in people who also take other antiviral medicines along with Videx to treat their HIV-1 infection and • who have never taken anti-HIV medicines before, and also in people who have taken antiviral medicines to treat their HIV-1 infection.   People who take Videx with the medicine stavudine (ZERIT®), and people with kidney problems may have an increased risk for developing pancreatitis. People who have advanced HIV-1 infection, especially the elderly, have an increased risk of developing pancreatitis. Your dose of Videx may need to be decreased by your healthcare provider, or your healthcare provider may need to hold or stop your treatment with Videx if you develop pancreatitis.   Before you start taking Videx, tell your healthcare provider if you: • have had pancreatitis • have kidney problems • drink alcoholic beverages • take the medicine stavudine (ZERIT)   Call your healthcare provider right away if you develop: • stomach-area (abdomen) pain • swelling of your stomach area • nausea and vomiting • fever 2. Build-up of acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take Videx alone or with other antiviral medicines. Lactic acidosis is a serious medical emergency that can lead to death. Death has happened in pregnant women who take Videx and the medicine stavudine (ZERIT), along with other antiviral medicines. The risk for lactic acidosis may be higher if you: • are pregnant • are taking stavudine (ZERIT) • have liver problems • are overweight • are taking HIV medicines for a long time   Lactic acidosis treatment usually requires hospitalization.   Lactic acidosis can be hard to identify early, because the symptoms could seem like symptoms of other health problems. Call your healthcare provider right away if you get the following symptoms which could be signs of lactic acidosis: • feel very weak or tired • have unusual (not normal) muscle pain • have trouble breathing • have stomach pain with nausea and vomiting • feel cold, especially in your arms and legs • feel dizzy or light-headed • have a fast or irregular heartbeat 3. Severe liver problems. Severe liver problems can happen in people, including pregnant women, who take Videx alone or with other antiviral medicines. In some cases, these severe liver problems can lead to the need for you to have a liver transplant, or cause death. Your liver may become large (hepatomegaly), you may develop fat in your liver (steatosis), liver failure, or high blood pressure in the large vein of your liver (portal hypertension). Your healthcare provider should examine you and check your liver function while you are taking Videx.   It is not known if Videx is safe and effective in people with HIV-infection who also have liver disease.   Call your healthcare provider right away if you develop: • yellowing of your skin or the white of your eyes (jaundice) • dark urine • pain on the right side of your stomach area (abdomen) • swelling of your stomach area • easy bruising or bleeding • loss of appetite • nausea or vomiting • vomiting of blood • dark-colored stools (bowel movements)   You may be more likely to develop severe liver problems if you: • are a woman • are pregnant • are overweight • have been treated for a long time with other medicines to treat HIV

What is Videx?

Videx is a prescription medicine used with other antiretroviral medicines to treat human immunodeficiency virus type 1 (HIV-1) infection in children and adults. Videx belongs to a class of drugs called nucleoside analogues.

When used with other HIV medicines, Videx may help:

• reduce the amount of HIV in your blood. This is called “viral load.” • increase the number of white blood cells called CD4+ (T) cells in your blood, which may help fight off other infections.

Reducing the amount of HIV-1 and increasing the CD4+ (T) cells in your blood may help improve your immune system. This may reduce your risk of death or getting infections that can happen when your immune system is weak (opportunistic infections).

Videx does not cure HIV-1 infection or AIDS. You must stay on continuous HIV-1 therapy to control infection and decrease HIV-related illnesses.

Avoid doing things that can spread HIV-1 infection to others.

• Do not share or re-use needles or other injection equipment. • Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades. • Do not have any kind of sex without protection. Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions, or blood.

Ask your healthcare provider if you have any questions about how to prevent passing HIV to other people.

Who should not take Videx?

Do not take Videx if you take:

• allopurinol (ZYLOPRIM®, LOPURIN®, ALOPRIM®) • ribavirin (COPEGUS®, REBETOL®, RIBASPHERE®, RIBAVIRIN®, VIRAZOLE®)

What should I tell my healthcare provider before taking Videx?

Before you take Videx, tell your healthcare provider if you:

• have had pancreatitis • have or had kidney problems • have or had liver problems (such as hepatitis) • have or had persistent numbness, tingling, or pain in the hands or feet (neuropathy) • drink alcoholic beverages • have any other medical conditions • are pregnant or plan to become pregnant. It is not known if Videx will harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking Videx. You and your healthcare provider will decide if you should take Videx while you are pregnant.
Pregnancy Registry: There is a pregnancy registry for women who take antiviral medicines 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 because of the risk of passing HIV to your baby. It is not known if Videx passes into your breast milk. 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. Videx may affect the way other medicines work, and other medicines may affect how Videx works.

Especially tell your healthcare provider if you take:

• tenofovir disoproxil fumarate (VIREAD®, ATRIPLA, COMPLERA, STRIBILD, TRUVADA) • hydroxyurea (DROXIA®, HYDREA®) • delavirdine mesylate (RESCRIPTOR®) • ganciclovir (CYTOVENE®, VALCYTE®) • indinavir (CRIXIVAN®) • methadone hydrochloride (DOLOPHINE® HYDROCHLORIDE, METHADOSE®) • nelfinavir (VIRACEPT®) • antacids that contain magnesium or aluminum • the antifungal medicines ketoconazole (NIZORAL®) and itraconazole (SPORANOX®, ONMEL) • a type of antibiotic called a “quinolone,” such as ciprofloxacin (CIPRO®) • an antibiotic that contains tetracycline • stavudine (ZERIT)

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

Ask your healthcare provider if you are not sure if you take one of the medicines listed above.

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. • Your healthcare provider may change your dose. Do not change your dose of Videx without talking to your healthcare provider. • Do not take Videx with food. Take Videx on an empty stomach at least 30 minutes before or 2 hours after you eat. • Videx comes as a Powder for Oral Solution. Your pharmacist will give you a bottle that contains Videx as a solution that has been mixed with acid-reducing medicines (antacids). • Shake the bottle well before taking each dose of Videx. • Be sure to close the bottle tightly after each use. • Try not to miss a dose of Videx, but if you do, take it as soon as possible. If it is almost time for the next dose, skip the missed dose. Then continue your regular dosing schedule. • Some medicines should not be taken at the same time of day that you take Videx. Check with your healthcare provider. • If your kidneys are not working well, your healthcare provider will need to do regular blood and urine tests to check how they are working while you take Videx. Your healthcare provider may also lower your dose of Videx if your kidneys are not working well. • If you take too much Videx, call a poison control center or go to an emergency room right away.

What are the possible side effects of Videx?

Videx can cause serious side effects.

• See “What is the most important information I should know about Videx?” • Vision changes. Contact your healthcare provider if you have changes in vision, such as dry eyes and/or blurred vision. You should have regular eye exams while you take Videx. • Nerve damage. Symptoms include numbness, tingling, or pain in your hands or feet. These are common with Videx, but are more likely to happen in people who have had these problems before, in people who take medicines that can affect the nerves, including stavudine (ZERIT), and in people who have advanced HIV disease. A child may not notice the symptoms. Ask your healthcare provider about the signs and symptoms of nerve problems that you should look for in your child during and after treatment with Videx. • Changes in your immune system (immune reconstitution syndrome) can happen when you start taking HIV-1 medicine. 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 new symptoms after starting to take HIV-1 medicine. • Changes in body fat can happen in people who take HIV-1 medicines. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the main part of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known.

The most common side effects of Videx include:

• diarrhea • stomach-area (abdomen) pain • nausea • vomiting • headache • rash

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Videx. For more information, ask your healthcare provider or pharmacist.

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.

If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Videx that is written for health professionals. For more information, go to www.bms.com/products/Pages/home.aspx or call 1-800-321-1335.

What are the ingredients in Videx?

Active ingredient: didanosine

Pediatric Oral Solution 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).

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by:
Bristol-Myers Squibb Company
Princeton, NJ 08543 USA

Product of Japan

1351316

Revised: August 2015

Videx® and Zerit® are registered trademarks of Bristol-Myers Squibb Company. All other trademarks are the property of their respective owners.

Applies to didanosine: oral delayed release capsule, oral powder for reconstitution, oral tablet chewable

General

The adverse effects of didanosine (the active ingredient contained in Videx) are sometimes difficult to distinguish from the symptomatology observed during the clinical course of AIDS, as well as from the possible adverse effects of other drugs used in the treatment of HIV infection. During the Expanded Access Program (EAP), adverse effects resulted in drug discontinuation in 42% of patients with AIDS and 34% of patients with ARC.

When didanosine is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when didanosine is used alone. Patients treated with didanosine in combination with stavudine, with or without hydroxyurea, may be at an increased risk for pancreatitis and hepatotoxicity, which may be fatal, and severe peripheral neuropathy.

Many of the side effects associated with nucleoside reverse transcriptase inhibitor therapy (myopathy, pancreatitis, liver failure, lactic acidosis, etc.) are attributable to their direct toxic effect on mitochondria which causes decreased mitochondrial energy-generating capacity.

Patients with renal dysfunction may be at increased risk of toxicity due to decreased clearance of didanosine.[Ref]

Gastrointestinal

Gastrointestinal side effects have included diarrhea (up to 70%), nausea (up to 53%), vomiting (30%), elevated lipase (Grades 3 to 4: up to 8%; all Grades: up to 26%), abdominal pain (up to 13%), and pancreatitis (up to 7%). Pancreatitis resulting in death has been reported during clinical trials of didanosine (the active ingredient contained in Videx) in combination with other antiretroviral agents. During the EAP in which patients received clinically recommended dosages, the incidence at 5 months for pancreatitis, increased amylase, or abdominal pain was 5% to 8%. Anorexia, dyspepsia, flatulence, pancreatitis (including fatal cases), dry mouth, sialoadenitis, and parotid gland enlargement have been reported during postmarketing experience.[Ref]

The frequency of pancreatitis is dose related. In phase 3 trials with buffered formulations, incidence ranged from 1% to 10% with doses higher than currently recommended and 1% to 7% with recommended doses.

The factors that increase the risk of pancreatitis in patients with HIV infection are an AIDS diagnosis, CD4+ cell count less than 100 cells/mm3, baseline hyperamylasemia, substantial alcohol intake, elevated liver transaminases, concurrent treatment with pancreatotoxic medications, and prior history. Resolution is generally seen 2 to 3 weeks following discontinuation of therapy, although fatal cases have been reported. Permanent discontinuation of didanosine in patients developing pancreatitis is suggested, because rechallenge often results in recurrent disease.

A retrospective cohort study evaluated the risk of pancreatitis with didanosine combination therapy. Patients with HIV can develop pancreatitis from the virus itself or from direct toxicity of several antiretroviral drugs.[Ref]

Hepatic

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretroviral agents. Caution should be exercised when administering didanosine (the active ingredient contained in Videx) to any patient with known risk factors for liver disease. However, cases have also been reported in patients with no known risk factors. Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents.

Hyperlactatemia and lactic acidosis are often a life-threatening and serious concern with the use of didanosine in combination with other antiretrovirals. Lactate elevation is a common issue in patients on stable antiretroviral therapy and increased levels without acidosis may result from increased production, release, or diminished clearance.

HIV reverse transcriptase inhibitors are competitive inhibitors of DNA polymerase and the greatest affinity appears to be in the mitochondria. Depletion of mitochondrial DNA diminishes cellular respiratory function leading to increased production of lactic acid. Excess lactic acid leaks out of the cell into systemic circulation and can progress to lactic acidosis if hydrogen ions drop the blood pH. Additionally, disturbances in metabolic homeostasis with antiretrovirals can cause hypertriglyceridemia and insulin resistance leading to steatohepatitis and decreased liver function.

Hyperlactatemia appears to be more common with didanosine while lactic acidosis is an infrequent occurrence.

In a report following patients on combined therapy with didanosine and tenofovir, one patient developed didanosine-related toxicity characterized by lactic acidosis with liver failure after 3 months on didanosine 200 mg/day with tenofovir.

Safety and efficacy 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 rate of liver function abnormalities, including severe and potentially fatal hepatic side effects.[Ref]

Hepatic side effects have included lactic acidosis/severe hepatomegaly with steatosis, hepatic toxicity, and elevated AST (Grades 3 to 4: up to 9%; all Grades: up to 53%), ALT (Grades 3 to 4: up to 9%; all Grades: up to 50%), bilirubin (Grades 3 to 4: up to 16%; all Grades: up to 68%), and gamma-glutamyltransferase (greater than 5 times ULN: up to 5%; all Grades: up to 28%). Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. In addition, fulminant hepatitis has been associated with didanosine and has resulted in death. Symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis, noncirrhotic portal hypertension, hepatitis, and liver failure have been reported during postmarketing experience. Hepatotoxicity and hepatic failure resulting in death have been reported during postmarketing experience with hydroxyurea and other antiretroviral agents.[Ref]

Nervous system

Peripheral neuropathy occurred in 16% of patients treated during the EAP. Early trials of didanosine (the active ingredient contained in Videx) therapy reported a higher incidence. Those studies, however, used higher dosages than more recent trials using lower therapeutic dosages and early trials included patients with very advanced HIV disease. One-year rates of developing peripheral neuropathy ranged from 6% to 15% in the latter trials.

Neuropathy presents as tingling, numbness, or pain in the hands or soles of the feet which progresses up the legs. The incidence is higher in patients with a history of neuropathy and/or low CD4+ cell counts (less than 50 cells/mm3). Following discontinuation of didanosine, neuropathy usually resolves within 2 to 12 weeks.[Ref]

Nervous system side effects have included headache (up to 46%), peripheral neurologic symptoms/neuropathy (up to 26%), insomnia, restlessness, and seizures.[Ref]

Metabolic

There has been one case report of acute gouty arthritis developing 14 weeks after didanosine (the active ingredient contained in Videx) was added to the treatment regimen of a patient receiving ritonavir, both known to infrequently cause hyperuricemia. The symptoms resolved upon discontinuation of didanosine and a short course of indomethacin.[Ref]

Metabolic side effects have included elevated alkaline phosphatase (greater than 5 times ULN: up to 4%), amylase (at least 1.4 times ULN: up to 17%; greater than 2 times ULN: up to 8%; all Grades: up to 31%), and uric acid (greater than 12 mg/dL: up to 3%). Hyperuricemia developed in 4% of patients treated during the EAP. At least one case of acute gouty arthritis has been reported. Diabetes mellitus, redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance"), hypoglycemia, hyperglycemia, and elevated serum uric acid, serum alkaline phosphatase, serum amylase, and serum gamma-glutamyltransferase have been reported during postmarketing experience.[Ref]

Dermatologic

Dermatologic side effects have included rash (up to 30%), rash/pruritus (up to 9%), and at least one case of cutaneous leukocytoclastic vasculitis. Alopecia has been reported during postmarketing experience.[Ref]

Hematologic

Hematologic side effects have included anemia, neutropenia, and thrombocytopenia. Leukopenia, anemia, and thrombocytopenia have also been reported during postmarketing experience. Thrombocytopenia and splenomegaly have been reported as early signs of noncirrhotic portal hypertension, which has been reported during postmarketing experience.[Ref]

Cardiovascular

Cardiovascular side effects have rarely included dyspnea, orthopnea, edema, pericarditis, and left ventricular failure. Underlying cardiomyopathy may have been aggravated by treatment with buffered formulations, which had high sodium content.[Ref]

Ocular

Ocular side effects have included retinal changes and optic neuritis. Diffuse dysfunction of the retinal epithelium with bilateral visual deficit (including night blindness and a peripheral visual fold reduction) has been reported. Dry eyes, retinal depigmentation, and optic neuritis have been reported during postmarketing experience.[Ref]

Diffuse dysfunction of the retinal epithelium has been reported in two patients during therapy with didanosine. Both patients experienced bilateral visual deficit including night blindness and a peripheral visual fold reduction. Symptoms were first noted after 31 and 34 weeks of therapy. Deficits in both patients appeared to be partially reversible upon discontinuation of didanosine.[Ref]

Other

Other side effects have included abdominal pain, asthenia, chills/fever, and pain during postmarketing experience.[Ref]

Musculoskeletal

Musculoskeletal side effects have included myalgia (with or without increases in creatine kinase), rhabdomyolysis (including acute renal failure and hemodialysis), arthralgia, and myopathy during postmarketing experience.[Ref]

Hypersensitivity

Hypersensitivity side effects have included anaphylactoid reaction during postmarketing experience.[Ref]

Immunologic

Immunologic side effects have included immune reconstitution syndrome. Autoimmune disorders (e.g., Graves' disease, polymyositis, and Guillain-Barre syndrome) have been reported in the setting of immune reconstitution.

Endocrine

Endocrine side effects are uncommon but have included hypertriglyceridemia, impaired glucose tolerance, hyperglycemia, and hypoglycemia. Insulin-dependent diabetes mellitus has also been reported.[Ref]

Some side effects of Videx may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.