Didanosine

Black Box Warnings

Fatal and nonfatal pancreatitis reported; suspend if pancreatitis suspected and discontinue if confirmed

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) reported with use of nucleoside analogues alone or in combination

Fatal lactic acidosis reported in pregnant women who have received didanosine and stavudine with other antiretroviral agents. Use the combination with caution in pregnant women

Contraindications

Hypersensitivity

Coadministration with allopurinol (may increase didanosine toxicity)

Coadministration with ribavirin (increases actrive metabolite dideoxyadenosine 5’-triphosphate levels, causing fatal hepatic failure, peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis)

Cautions

(All NRTIs): Risk of potentially fatal lactic acidosis & severe hepatomegaly with steatosis when used alone or in combination with other antiretrovirals

Risk of potentially fatal pancreatitis, increases if used in combo with stavudine

Risk of potentially fatal bleeding from esophageal varices in patients with non-cirrhotic portal hypertension

Discontinue if pancreatitis occurs; reduce dose for other ADR's

Risk of immune reconstitution syndrome if used in combination w/ other antiretroviral drugs

Risk of retinal changes and optic neuritis

Rapidly degrades in acidic pH, however, EC is protected from stomach acids

Noncirrhotic portal hypertension reported; discontinue if signs/symptoms occur (eg, elevated liver enzymes, esophageal varices, hematemesis, ascites, splenomegaly)

Coadministration of methadone with Videx pediatric powder may significant decrease didanosine concentrations

Pregnancy Category: B

Lactation: Not known whether distributed into 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.

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Powder for Oral Solution Preparation

Prior to dispensing, the pharmacist must reconstitute dry powder to an initial concentration of 20 mg/mL and immediately mix the resulting solution with antacid to a final concentration of 10 mg/mL

Initial solution (20 mg/mL): 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 powder, respectively

Final solution (10 mg/mL): Immediately mix one part of the 20 mg/mL initial solution with one part of any commercially available antacid that contains as active ingredients aluminum hydroxide (400 mg/5 mL), magnesium hydroxide (400 mg/5 mL), and simethicone (40 mg/5 mL) for a final dispensing concentration of 10 mg/mL

Oral Administration

Oral solution dispensed as 10 mg/mL with antacid as diluent

Take on empty stomach, at least 30 minutes before food or 2 hr after food; Cmax and AUC reduced by ~46% and 19% respectively in the presence of food

EC not approved for aged <6 yr and for children who weigh <20 kg and unable to swallow capsule whole

Storage

Reconstituted oral solution (10 mg/mL): Refrigerate for up to 30 days at 36-46°F (2-8°C); discard any unused portion after 30 days

The most severe side effects of didanosine are:

• inflammation of the pancreas (pancreatitis),
• liver failure, and
• nerve damage in the arms and legs (peripheral neuropathy).

Symptoms of peripheral neuropathy are tingling, numbness and pain in the feet or hands.

Other important side effects include:

• diarrhea,
• chills,
• fever,
• rash, stomach pain,
• headache,
• nausea and vomiting.

Although it is not known whether didanosine is excreted in breast milk, HIV-infected mothers should not breast feed because of the potential risk of transmitting HIV to an infant that is not infected.

Capsules (Extended Release): 125, 200, 250, and 400 mg. Solution: 10 mg/ml

Capsules and unmixed powder should be stored at room temperature, 15 C to 30 C (59 F to 86 F). The powder may be stored in the refrigerator at 2 C to 8 C (36 F to 46 F for up to 30 days after it is mixed with water.

The most common side effects of didanosine include:

• diarrhea
• stomach pain
• nausea
• vomiting
• headache
• rash

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

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

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

Before you take didanosine, 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. 

WARNING: PANCREATITIS, LACTIC ACIDOSIS and HEPATOMEGALY with STEATOSIS

Fatal and nonfatal pancreatitis has occurred during therapy with didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Didanosine should be suspended in patients with suspected pancreatitis and discontinued in patients with confirmed pancreatitis.

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. 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.

Didanosine is an antiviral medicine that prevents human immunodeficiency virus (HIV) from multiplying in your body.

Didanosine is used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). Didanosine is not a cure for HIV or AIDS.

Didanosine is for use in adults and children who are at least 2 weeks old.

Didanosine may also be used for purposes not listed in this medication guide.

Usual Adult Dose for HIV Infection:

Delayed-release capsules:
Less than 60 kg: 250 mg orally once a day
60 kg or more: 400 mg orally once a day

Oral solution:
Preferred dosing:
Less than 60 kg: 125 mg orally twice a day
60 kg or more: 200 mg orally twice a day

For patients requiring once-daily dosing:
Less than 60 kg: 250 mg orally once a day
60 kg or more: 400 mg orally once a day

Usual Adult Dose for Nonoccupational Exposure:

(Not approved by FDA)

Centers for Disease Control and Prevention recommendations:
Delayed-release capsules:
Less than 60 kg: 250 mg orally once a day
60 kg or more: 400 mg orally once a day

Oral solution:
Preferred dosing:
Less than 60 kg: 125 mg orally twice a day
60 kg or more: 200 mg orally twice a day

For patients requiring once-daily dosing:
Less than 60 kg: 250 mg orally once a day
60 kg or more: 400 mg orally once a day

Duration: 28 days

Prophylaxis should be initiated as soon as possible, within 72 hours of exposure. In general, the alternative regimens recommended for nonoccupational postexposure HIV prophylaxis include didanosine as part of protease inhibitor (PI)-based regimens.

Usual Pediatric Dose for HIV Infection:

Delayed-release capsules:
20 to less than 25 kg: 200 mg orally once a day
25 to less than 60 kg: 250 mg orally once a day
60 kg or more: 400 mg orally once a day

Oral solution:
2 weeks to 8 months: 100 mg/m2 orally twice a day
9 months to 18 years: 120 mg/m2 orally twice a day; adult dose should not be exceeded

Tell your doctor about all your current medicines and any you start or stop using, especially:

• ganciclovir;

• hydroxyurea;

• methadone;

• tetracycline;

• tenofovir; or

• medicines that should not be taken at the same time as didanosine--ciprofloxacin, delavirdine, indinavir, itraconazole, ketoconazole, or nelfinavir.

This list is not complete. Other drugs may interact with didanosine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For didanosine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to didanosine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of didanosine in children 2 weeks of age and older.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of didanosine in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving didanosine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking didanosine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using didanosine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Allopurinol
• Oxypurinol
• Ribavirin

Using didanosine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Darunavir
• Hydroxyurea
• Orlistat
• Stavudine
• Tenofovir Disoproxil Fumarate
• Zalcitabine

Using didanosine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atazanavir
• Atevirdine
• Ciprofloxacin
• Delavirdine
• Enoxacin
• Ganciclovir
• Indinavir
• Itraconazole
• Ketoconazole
• Lomefloxacin
• Methadone
• Metoclopramide
• Moxifloxacin
• Nelfinavir
• Norfloxacin
• Ofloxacin
• Ranitidine
• Rifabutin
• Ritonavir
• Sulfamethoxazole
• Trimethoprim
• Trovafloxacin Mesylate
• Valganciclovir

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of didanosine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol use, active or history of or
• Liver disease (including hepatitis) or
• Obesity (overweight) or
• Pancreatitis (inflammation of the pancreas), history of or
• Peripheral neuropathy (nerve disorder), history of—Use with caution. May cause side effects to become worse.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Portal hypertension (high blood pressure in the portal vein of the liver)—Use with caution. May make this condition worse.

Take didanosine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not stop taking didanosine without checking first with your doctor.

didanosine comes with a Medication Guide. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

Keep taking didanosine for the full time of treatment, even if you begin to feel better. Only take medicine that your doctor has prescribed specifically for you. Do not share your medicine with other people.

didanosine works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. If you need help in planning the best times to take your medicine, check with your doctor.

Didanosine should be taken on an empty stomach since food may keep it from working properly. Didanosine oral liquid should be taken at least 30 minutes before or 2 hours after you eat.

Swallow the delayed-release capsule whole. Do not break, crush, chew, or open it.

Shake the oral liquid before use. Measure each dose with a specially marked measuring spoon or measuring cup. The average household teaspoon may not hold the right amount of liquid.

Dosing

The dose of didanosine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of didanosine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For HIV infection:
  • For oral dosage form (delayed-release capsules):
    • Adults, teenagers, and children who can swallow capsules—Dose is based on body weight and must be determined by your doctor.
      • For patients weighing 60 kilograms (kg) or more—400 milligrams (mg) once a day.
      • For patients weighing 25 kg to less than 60 kg—250 mg once a day.
      • For patients weighing 20 kg to less than 25 kg—200 mg once a day.
    • Children weighing less than 20 kg—The oral capsules are not given to small children.
  • For oral dosage form (solution):
    • Adults weighing 60 kilograms (kg)—Dose is based on body weight and must be determined by your doctor. The usual dose is 200 milligrams (mg) two times a day or 400 mg once a day.
    • Adults weighing less than 60 kg—Dose is based on body weight and must be determined by your doctor. The usual dose is 125 mg two times a day or 250 mg once a day.
    • Teenagers, children, and infants 8 months of age and older—Dose is based on body size and must be determined by your doctor. The usual dose is 120 milligrams per square meter (mg/m(2)) two times a day.
    • Infants 2 weeks to 8 months old—Dose is based on body size and must be determined by your doctor. The usual dose is 100 mg/m(2) two times a day.
    • Infants younger than 2 weeks old—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of didanosine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the delayed-release capsules in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Store the oral liquid in the refrigerator. Throw away any unused medicine after 30 days.

It is very important that your doctor check your or your child's progress at regular visits to make sure that didanosine is working properly. Blood tests may be needed to check for unwanted effects.

Do not use didanosine if you or your child are also using allopurinol (Zyloprim®) or ribavirin (Copegus®, Rebetol®). Using these medicines together may cause serious side effects.

didanosine may cause a life-threatening condition called pancreatitis. Check with your doctor right away if you or your child have more than one of these symptoms: bloating, chills, constipation, darkened urine, a fast heartbeat, fever, indigestion, loss of appetite, nausea, pains in the stomach, side, or abdomen, possibly radiating to the back, vomiting, or yellow eyes or skin.

Two rare but serious reactions to didanosine are lactic acidosis (too much acid in the blood) and liver toxicity, which includes an enlarged liver. These are more common if you are female, very overweight (obese), or have been taking anti-HIV medicines for a long time. Call your doctor right away if you or your child have more than one of these symptoms: abdominal or stomach discomfort or cramping, dark urine, decreased appetite, diarrhea, a general feeling of discomfort, light-colored stools, muscle cramping or pain, nausea, unusual tiredness or weakness, trouble breathing, vomiting, or yellow eyes or skin.

Check with your doctor right away if you or your child have abdominal or stomach pain, black, tarry stools, bleeding gums, blood in the urine or stools, pinpoint red spots on the skin, or unusual bleeding or bruising. These may be symptoms of a condition called non-cirrhotic portal hypertension.

Tell your doctor right away if you or your child start having numbness, tingling, or burning pain in your hands, arms, legs, or feet. These may be symptoms of a condition called peripheral neuropathy.

Your immune system may get stronger when you start taking HIV medicines. Sometimes the immune system will start to fight infections that were hidden in your body, such as pneumonia or tuberculosis. Tell your doctor right away if you notice any changes in your health.

didanosine may cause you or your child to have excess body fat. Tell your doctor right away if you notice changes in your body shape, including an increased amount of body fat in the neck or upper back, face, around the chest, or stomach area. You might also lose fat from your legs, arms, or face.

Check with your doctor right away if you or your child start to see unusual colors or have blurred vision. Your doctor may want you to have your eyes checked regularly by an eye doctor (ophthalmologist).

Do not drink alcohol while you are using didanosine.

HIV may be acquired from or spread to other people through infected body fluids, including blood, vaginal fluid, or semen. If you are infected, it is best to avoid any sexual activity involving an exchange of body fluids with other people. If you do have sex, always wear (or have your partner wear) a condom (“rubber”). Only use condoms made of latex, and use them every time you have vaginal, anal, or oral sex. The use of a spermicide (such as nonoxynol-9) may also help prevent transmission of HIV if it is not irritating to the vagina, rectum, or mouth. Spermicides have been shown to kill HIV in lab tests. Do not use oil-based jelly, cold cream, baby oil, or shortening as a lubricant—these products can cause the condom to break. Lubricants without oil, such as K-Y jelly, are recommended. Women may wish to carry their own condoms. Birth control pills and diaphragms will help protect against pregnancy, but they will not prevent someone from giving or getting the AIDS virus. If you inject drugs, get help to stop. Do not share needles or equipment with anyone. In some cities, more than half of the drug users are infected and sharing even 1 needle or syringe can spread the virus. If you have any questions about this, check with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Nausea and vomiting
• stomach pain
• tingling, burning, numbness, and pain in the hands or feet

• Convulsions (seizures)
• fever and chills
• shortness of breath
• skin rash and itching
• sore throat
• swelling of the feet or lower legs
• unusual bleeding and bruising
• unusual tiredness and weakness
• yellow skin and eyes

• Abdominal or stomach discomfort
• anxiety
• black, tarry stools
• bleeding gums
• blindness
• bloating
• blood in the urine or stools
• blue-yellow color blindness
• blurred vision
• change in the color of the eye
• chest pain
• clay colored stools
• cold sweats
• coma
• confusion
• constipation
• cool, pale skin
• cough
• dark urine
• decreased appetite
• decreased vision
• depression
• diarrhea
• difficulty with moving
• difficulty with swallowing
• dizziness
• dry eyes
• dry mouth
• eye pain
• fast heartbeat
• fast, shallow breathing
• flushed, dry skin
• fruit-like breath odor
• general feeling of discomfort
• headache
• hives
• increased hunger
• increased thirst
• increased urination
• indigestion
• joint pain
• light-colored stools
• loss of appetite
• loss of consciousness
• muscle aching, cramping, or pain
• nightmares
• painful or difficult urination
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• right upper abdominal or stomach pain and fullness
• shakiness
• sleepiness
• slurred speech
• sores, ulcers, or white spots on the lips or in the mouth
• stomachache
• sweating
• swollen glands
• swollen joints
• tightness in the chest
• troubled breathing with exertion
• unexplained weight loss
• unsteadiness or awkwardness
• weakness in the arms, hands, legs, or feet

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Difficulty with sleeping
• irritability
• restlessness

• Acid or sour stomach
• belching
• excess air or gas in the stomach or intestines
• full feeling
• hair loss or thinning of the hair
• heartburn
• indigestion
• lack or loss of strength
• passing gas
• redistribution or accumulation of body fat

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

Pancreatitis

Fatal and nonfatal pancreatitis has occurred during therapy with Didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Didanosine delayed-release capsules should be suspended in patients with signs or symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Patients treated with Didanosine delayed-release capsules in combination with stavudine may be at increased risk for pancreatitis.

When treatment with life-sustaining drugs known to cause pancreatic toxicity is required, suspension of Didanosine delayed-release capsules therapy is recommended. In patients with risk factors for pancreatitis, Didanosine delayed-release capsules 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 (6)].

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. 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 [see Use in Specific Populations (8.1)]. Particular caution should be exercised when administering Didanosine delayed-release capsules 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 Didanosine delayed-release capsules 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 Didanosine delayed-release capsules 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. This combination should be avoided [see Adverse Reactions (6)].

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 Didanosine delayed-release capsules should be monitored for early signs of portal hypertension (e.g., 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. Didanosine delayed-release capsules should be discontinued in patients with evidence of non-cirrhotic portal hypertension.

Peripheral Neuropathy

Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in patients receiving Didanosine 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, including stavudine. Discontinuation of Didanosine delayed-release capsules should be considered in patients who develop peripheral neuropathy [see Adverse Reactions (6)].

Retinal Changes and Optic Neuritis 

Retinal changes and optic neuritis have been reported in patients taking Didanosine. Periodic retinal examinations should be considered for patients receiving Didanosine delayed-release capsules [see Adverse Reactions (6)].

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Didanosine delayed-release capsules. 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-Barré 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.

Fat Redistribution 

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

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 Didanosine in adult and pediatric patients [see Dosage and Administration (2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)]. Additional pharmacokinetic studies in pediatric patients support use of Didanosine delayed-release capsules in pediatric patients who weigh at least 20 kg.

Geriatric Use

In an Expanded Access Program using a buffered formulation of Didanosine for the treatment of 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, including those for Didanosine delayed-release capsules, 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/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)].

Didanosine delayed-release capsules USP are an enteric-coated formulation of Didanosine, USP, a synthetic purine nucleoside analogue active against HIV-1. Each Didanosine delayed-release capsule containing enteric-coated pellets, for oral administration, contains 200 mg, 250 mg or 400 mg of Didanosine, USP.  In addition each capsule contains the following inactive ingredients: black iron oxide, croscarmellose sodium, D&C yellow no. 10 aluminum lake, FD&C blue no. 1, FD&C blue no. 1 aluminum lake, FD&C blue no. 2 aluminum lake, FD&C red no. 40 aluminum lake, gelatin, hydroxypropyl cellulose, hypromellose, methacrylic acid copolymer dispersion, microcrystalline cellulose, polydextrose, polyethylene glycol, propylene glycol, shellac glaze, silicon dioxide, sodium hydroxide, talc, titanium dioxide, triacetin and triethyl citrate.  The 200 mg and 400 mg capsule also contains D&C red no. 33 and FD&C yellow no. 6, and the 250 mg also contains D&C red no. 28.

The chemical name for Didanosine is 2’,3’ -dideoxyinosine. The structural formula is:

C10H12N4O3 M.W. 236.2

Didanosine is a white crystalline powder. The aqueous solubility of Didanosine at 25°C and pH of approximately 6 is 27.3 mg/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. In Didanosine delayed-release capsules USP, an enteric coating is used to protect Didanosine from degradation by stomach acid.

Mean Cmax and AUC were 19% and 13% higher, respectively.

Pediatric powder for oral solution: Prior to dispensing, add 100 mL or 200 mL purified water, USP to the 2 g or 4 g container, respectively, to achieve a 20 mg/mL solution. Immediately mix the resulting solution with an equal volume of antacid that contains the active ingredients aluminum hydroxide (400 mg/5 mL), magnesium hydroxide (400 mg/5 mL) and simethicone (40 mg/5 mL) to achieve a final concentration of 10 mg/mL. Dispense in flint glass or plastic (eg, HDPE, PET or PETG) bottles with child resistant closures.

LactMed Record Number

652

Last Revision Date

20170110

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