Didanosine Tablet, for suspension
Name: Didanosine Tablet, for suspension
- Didanosine Tablet, for suspension 100 mg
- Didanosine Tablet, for suspension tablet
- Didanosine Tablet, for suspension 12 mg
- Didanosine Tablet, for suspension drug
- Didanosine Tablet, for suspension mg
- Didanosine Tablet, for suspension side effects
- Didanosine Tablet, for suspension dosage
- Didanosine Tablet, for suspension 200 mg
Dosage Forms and Strengths
Didanosine Tablets for Oral Suspension, 100 mg are white to off-white, slightly mottled, round, flat faced beveled edge tablets with debossing “D” on one side and “45” on other side. The tablets are packaged in bottles with child-resistant closures.
Didanosine Tablets for Oral Suspension, 150 mg are white to off-white, slightly mottled, round, flat faced beveled edge tablets with debossing “D” on one side and “46” on other side. The tablets are packaged in bottles with child-resistant closures.
Didanosine Tablets for Oral Suspension, 200 mg are white to off-white, slightly mottled, round, flat faced beveled edge tablets with debossing “D” on one side and “47” on other side. The tablets are packaged in bottles with child-resistant closures.
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections:
- 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 didanosine are provided in Tables 4 and 5.
| Adverse Reactions | Percent of Patients* | |||
|---|---|---|---|---|
| ACTG 116A | ACTG 116B/117 | |||
| didanosine n=197 | zidovudine n=212 | didanosine 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 |
| Percent of Patientsa,c | ||||
|---|---|---|---|---|
| AI454-148b | START 2b | |||
| didanosine + stavudine + nelfinavir n=482 | zidovudine + lamivudine + nelfinavir n=248 | didanosine + 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 didanosine plus stavudine plus nelfinavir in Study AI454-148 and in one patient who received didanosine plus stavudine plus indinavir in the START 2 study. In addition, pancreatitis resulting in death was observed in 2 of 68 patients who received didanosine 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 didanosine are shown in Tables 6 to 8.
| Parameter | Percent of Patients | |||
|---|---|---|---|---|
| ACTG 116A | ACTG 116B/117 | |||
| didanosine n=197 | zidovudine n=212 | didanosine 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 |
| Parameter | Percent of Patientsa | |||
|---|---|---|---|---|
| AI454-148b | START 2b | |||
| didanosine + stavudine + nelfinavir n=482 | zidovudine + lamivudine + nelfinavir n=248 | didanosine + 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 |
| Parameter | Percent of Patientsa | |||
|---|---|---|---|---|
| AI454-148b | START 2b | |||
| didanosine + stavudine + nelfinavir n=482 | zidovudine + lamivudine + nelfinavir n=248 | didanosine + 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/m2/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/m2 every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg/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, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to didanosine, 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)], sialoadenitis, 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 didanosine 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 didanosine and hydroxyurea, with or without stavudine, should be avoided.
Drug Interactions
Established Drug Interactions
Clinical recommendations based on the results of drug interaction studies are listed in Table 9. Pharmacokinetic results of drug interaction studies are shown in Tables 13 and 14 [see Contraindications (4.1 and 4.2), Clinical Pharmacology (12.3)].
| Drug | Effect | Clinical Comment |
|---|---|---|
| ↑ Indicates increase. ↓ Indicates decrease. a The dosing recommendation for coadministration of didanosine delayed-release capsules and tenofovir disoproxil fumarate with respect to meal consumption differs from that of didanosine. See the complete prescribing information for didanosine delayed-release capsules. | ||
| ciprofloxacin | ↓ ciprofloxacin concentration | Administer didanosine at least 2 hours after or 6 hours before ciprofloxacin. |
| delavirdine | ↓ delavirdine concentration | Administer didanosine 1 hour after delavirdine. |
| ganciclovir | ↓ didanosine concentration | If there is no suitable alternative to ganciclovir, then use in combination with didanosine with caution. Monitor for didanosine-associated toxicity. |
| indinavir | ↓ indinavir concentration | Administer didanosine 1 hour after indinavir. |
| methadone | ↓ didanosine concentration | Do not coadminister methadone with didanosine pediatric powder due to significant decreases in didanosine concentrations. If coadministration of methadone and didanosine is necessary, the recommended formulation of didanosine is didanosine delayed-release capsules. Patients should be closely monitored for adequate clinical response when didanosine delayed-release capsules are coadministered with methadone, including monitoring for changes in HIV RNA viral load. |
| nelfinavir | ↓ No interacion 1 hour after didanosine | Administer nelfinavir 1 hour after didanosine. |
| tenofovir disoproxil fumarate | ↓ didanosine concentration | A dose reduction of didanosine to the following dosage once daily is recommended.a
|
Exposure to didanosine is increased when coadministered with tenofovir disoproxil fumarate [Table 9 and see Clinical Pharmacology (12.3, Table 13)]. 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 didanosine should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities and clinical response. Didanosine should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop [see Dosage and Administration (2.3), Warnings and Precautions (5)]. 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 didanosine are listed in Table 10.
| Drug or Drug Class | Effect | Clinical Comment |
|---|---|---|
| ↑ Indicates increase. ↓ Indicates decrease. 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 didanosine is recommended [see Warnings and Precautions (5.1)]. b[See Warnings and Precautions (5.6).] | ||
| 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 didanosine tablets for oral suspension and didanosine pediatric powder for oral solution |
| Azole antifungals | ↓ ketoconazole or Itraconazole concentration | Administer drugs such as ketoconazole or itraconazole at least 2 hours before didanosine. |
| Quinolone antibiotics (see also ciprofloxacin in Table 9) | ↓ quinolone concentration | Consult package insert of the quinolone. |
| Tetracycline antibiotics | ↓ antibiotic concentration | Consult package insert of the tetracycline. |
How Supplied/Storage and Handling
Didanosine Tablets for Oral Suspension USP, 100 mg are white to off-white, slightly mottled, round, flat faced beveled edge tablets with debossing “D” on one side and “45” on other side. The tablets are packaged in bottles with child-resistant closures.
Bottles of 60 NDC 65862-092-60
Didanosine Tablets for Oral Suspension USP, 150 mg are white to off-white, slightly mottled, round, flat faced beveled edge tablets with debossing “D” on one side and “46” on other side. The tablets are packaged in bottles with child-resistant closures.
Bottles of 60 NDC 65862-093-60
Didanosine Tablets for Oral Suspension USP, 200 mg are white to off-white, slightly mottled, round, flat faced beveled edge tablets with debossing “D” on one side and “47” on other side. The tablets are packaged in bottles with child-resistant closures.
Bottles of 60 NDC 65862-094-60
Storage
Store in tightly closed bottles at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. If dispersed in water, the dose may be held for up to 1 hour at ambient temperature.
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 100 mg (60 Tablet Bottle)
NDC 65862-092-60
Didanosine Tablets for
Oral Suspension, USP
[Formerly: Didanosine Tablets
(Chewable, Dispersible, Buffered)]
100 mg
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
Rx only 60 Tablets
AUROBINDO
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 200 mg (60 Tablet Bottle)
NDC 65862-094-60
Didanosine Tablets for
Oral Suspension, USP
[Formerly: Didanosine Tablets
(Chewable, Dispersible, Buffered)]
200 mg
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
Rx only 60 Tablets
AUROBINDO
| DIDANOSINE Didanosine Tablet, for suspension | ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| DIDANOSINE Didanosine Tablet, for suspension | ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| DIDANOSINE Didanosine Tablet, for suspension | ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| ||||||||||||||||||||
| Labeler - Aurobindo Pharma Limited (650082092) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Aurobindo Pharma Limited | 918917642 | ANALYSIS(65862-092, 65862-093, 65862-094), MANUFACTURE(65862-092, 65862-093, 65862-094) | |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Aurobindo Pharma Limited | 918917662 | API MANUFACTURE(65862-092, 65862-093, 65862-094) | |