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Didanosine


General


Pronunciation

(dye DAN oh seen)


Brand Names: U.S.

  • Videx
  • Videx EC

Indications


Use: Labeled Indications

HIV infection: Treatment of HIV-1 infection in combination with other antiretroviral agents.


Contraindications


Coadministration with allopurinol or ribavirin

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to didanosine or any component of the formulation


ALERT: U.S. Boxed Warning

Pancreatitis:

Fatal and nonfatal pancreatitis have occurred during therapy with didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of the degree of immunosuppression. Suspend didanosine in patients with suspected pancreatitis; discontinue didanosine in patients with confirmed pancreatitis.

Lactic acidosis/severe hepatomegaly:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs 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. Use the combination of didanosine and stavudine with caution during pregnancy; the combination is recommended only if the potential benefit clearly outweighs the potential risk.


Dosing and Administration


Dosing: Adult

Treatment of HIV infection: Oral:

Dosing based on patient weight:

Pediatric powder for oral solution (Videx):

<60 kg: 125 mg twice daily (preferred) or 250 mg once daily

≥60 kg: 200 mg twice daily (preferred) or 400 mg once daily

Delayed release capsule (Videx EC):

25 kg to <60 kg: 250 mg once daily

≥60 kg: 400 mg once daily

Dosage adjustment for concomitant therapy:

When taken with tenofovir:

<60 kg and CrCl ≥60 mL/minute: 200 mg once daily

≥60 kg and CrCl ≥60 mL/minute: 250 mg once daily


Dosing: Geriatric

Refer to adult dosing. Elderly patients have a higher frequency of pancreatitis (10% versus 5% in younger patients); monitor renal function and dose accordingly.


Dosing: Pediatric

Treatment of HIV infection: Oral:

Pediatric powder for oral solution (Videx): Note: Once-daily dosing of the oral solution is not FDA approved in children.

Infants: 2 weeks to 8 months: 100 mg/m2 twice daily is recommended by the manufacturer; 50 mg/m2 may be considered in infants 2 weeks to <3 months (HHS [pediatric], 2014)

Infants and Children >8 months: 120 mg/m2 twice daily, not to exceed adult dose, is recommended by the manufacturer.

Adolescents: Dosing based on patient weight: Refer to adult dosing.

Children 3 to 21 years (off-label dose): Treatment-naive: 240 mg/m2/dose once daily (maximum: 400 mg/dose) (HHS [pediatric], 2014)

Delayed release capsule (Videx EC):

Children ≥6 years:

20 kg to <25 kg: 200 mg once daily

25 kg to <60 kg: 250 mg once daily

≥60 kg: 400 mg once daily

Children 3 to 21 years (off-label dose): Treatment-naive: 240 mg/m2/dose once daily (maximum: 400 mg/dose) (HHS [pediatric], 2014)


Dosing: Renal Impairment

Adults: Dosing based on patient weight, creatinine clearance, and dosage form: See table.

Recommended Dose (mg) of Didanosine by Body Weight ¢ ˆ ’ Adults

Creatinine Clearance (mL/min)

≥60 kg

<60 kg

Powder for Oral Solution

Delayed Release Capsule

Powder for Oral Solution

Delayed Release Capsule

Note: Per manufacturer, not suitable for use in patients <60 kg with CrCr <10 mL/minute; use alternate formulation.

≥60

400 mg daily or 200 mg twice daily

400 mg daily

250 mg daily or 125 mg twice daily

250 mg daily

30-59

200 mg daily or 100 mg twice daily

200 mg daily

150 mg daily or 75 mg twice daily

125 mg daily

10-29

150 mg daily

125 mg daily

100 mg daily

125 mg daily

<10

100 mg daily

125 mg daily

75 mg daily

See Note.

Table has been converted to the following text.

Recommended Didanosine Dose by Body Weight ¢ ˆ ’ Adults

DOSING FOR ≥60 kg:

CrCl ≥60 mL/minute:

- Capsule, delayed release: 400 mg once daily

- Powder for oral solution: 400 mg once daily or 200 mg twice daily

CrCl 30-59 mL/minute:

- Capsule, delayed release: 200 mg once daily

- Powder for oral solution: 200 mg once daily or 100 mg twice daily

CrCl 10-29 mL/minute:

- Capsule, delayed release: 125 mg once daily

- Powder for oral solution: 150 mg once daily

CrCl <10 mL/minute:

- Capsule, delayed release: 125 mg once daily

- Powder for oral solution: 100 mg once daily

DOSING FOR PATIENTS <60 kg:

CrCl ≥60 mL/minute:

- Capsule, delayed release: 250 mg once daily

- Powder for oral solution: 250 mg once daily or 125 mg twice daily

CrCl 30-59 mL/minute:

- Capsule, delayed release: 125 mg once daily

- Powder for oral solution: 150 mg once daily or 75 mg twice daily

CrCl 10-29 mL/minute:

- Capsule, delayed release: 125 mg once daily

- Powder for oral solution: 100 mg once daily

CrCl <10 mL/minute:

- Capsule, delayed release: Per manufacturer, not suitable for use in patients <60 kg with CrCl <10 mL/minute; use alternate formulation.

- Powder for oral solution: 75 mg once daily

Patients requiring hemodialysis or CAPD: Dose per CrCl <10 mL/minute. Didanosine is not removed via CAPD and minimal amount of dose ( ≤7%) is removed by hemodialysis; no supplemental dosing necessary.

Children: No specific guidelines available; consider dosage reduction using adjustments for adults.


Dosing: Hepatic Impairment

No dosage adjustment necessary.


Reconstitution

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.


Administration

Oral: Pediatric powder for oral solution: Administer on an empty stomach at least 30 minutes before or 2 hours after eating. Shake well prior to use.

Oral: Videx EC: Administer on an empty stomach at least 30 minutes before or 2 hours after eating; swallow capsule whole.


Dietary Considerations

Take on an empty stomach; administer at least 30 minutes before or 2 hours after eating


Storage

Delayed release capsules should be stored in tightly closed bottles at controlled room temperature of 25 ‚ °C (77 ‚ °F). Unreconstituted powder should be stored at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F); reconstituted oral solution is stable for 30 days stored at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Delayed Release, Oral:

Videx EC: 125 mg, 200 mg, 250 mg, 400 mg

Generic: 125 mg, 200 mg, 250 mg, 400 mg

Solution Reconstituted, Oral:

Videx: 2 g (100 mL); 4 g (200 mL)


Drug Interactions

Alcohol (Ethyl): May enhance the adverse/toxic effect of Didanosine. Specifically, the risk of pancreatitis may be increased. Avoid combination

Allopurinol: May increase the serum concentration of Didanosine. Avoid combination

Antifungal Agents (Azole Derivatives, Systemic): Didanosine may decrease the absorption of Antifungal Agents (Azole Derivatives, Systemic). Enteric coated didanosine capsules are not expected to affect these antifungals. Exceptions: Isavuconazonium Sulfate. Consider therapy modification

Atazanavir: Didanosine may decrease the serum concentration of Atazanavir. Specifically, the buffered formulation of didanosine may decrease atazanavir absorption. Atazanavir may decrease the serum concentration of Didanosine. Reported with enteric coated didanosine capsules. Management: To avoid therapeutic failure of atazanavir the drug should be administered 2 hours before or 1 hour after didanosine. This recommendation applies to both buffered didanosine products and enteric coated didanosine products. Consider therapy modification

Darunavir: May decrease the serum concentration of Didanosine. More specifically, this interaction is likely due to the effects of food (with which darunavir/ritonavir are taken) on didanosine, which is supposed to be given on an empty stomach. Management: Didanosine should be administered 1 hour prior to or 2 hours after administration of darunavir/ritonavir (which must be taken with food). Consider therapy modification

Febuxostat: May increase the serum concentration of Didanosine. Avoid combination

Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity with zidovudine is of particular concern. Ganciclovir-Valganciclovir may increase the serum concentration of Reverse Transcriptase Inhibitors (Nucleoside). Management: Monitor patients receiving any of these combination closely for toxicity of the reverse transcriptase inhibitor. Avoid zidovudine. Intravitreal implants would not be affected. Consider therapy modification

Hydroxyurea: May enhance the adverse/toxic effect of Didanosine. An increased risk of pancreatitis, hepatotoxicity and/or neuropathy may exist. Didanosine may enhance the adverse/toxic effect of Hydroxyurea. An increased risk of pancreatitis, hepatotoxicity and/or neuropathy may exist. Avoid combination

Indinavir: Didanosine may decrease the serum concentration of Indinavir. Management: Indinavir should be administered on an empty stomach at least 1 hour apart from administration of buffer-containing formulations of didanosine. Consider therapy modification

Lopinavir: May decrease the serum concentration of Didanosine. This interaction refers only to lopinavir/ritonavir oral solution, which must be taken with food, and is principally the result of a food-didanosine interaction. Management: Didanosine should be administered 1 hour prior to or 2 hours after administration of lopinavir/ritonavir oral solution (which must be taken with food). Didanosine and lopinavir/ritonavir tablets can be administered together. Consider therapy modification

Methadone: May decrease the serum concentration of Didanosine. Management: If use of methadone with didanosine is necessary, enteric coated didanosine is preferred. Avoid using didanosine powder for solution with methadone. Increased monitoring of clinical response to didanosine (including viral load) is necessary. Consider therapy modification

Quinolone Antibiotics: May decrease the serum concentration of Didanosine. Didanosine may decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after didanosine. Monitor for decreased therapeutic effects of quinolones, particularly if doses cannot be separated as recommended. This does not apply to unbuffered enteric coated didanosine. Exceptions: LevoFLOXacin (Oral Inhalation). Consider therapy modification

Ribavirin (Oral Inhalation): May enhance the adverse/toxic effect of Didanosine. Ribavirin (Oral Inhalation) may increase serum concentrations of the active metabolite(s) of Didanosine. Avoid combination

Ribavirin (Systemic): May enhance the adverse/toxic effect of Didanosine. Ribavirin (Systemic) may increase serum concentrations of the active metabolite(s) of Didanosine. Avoid combination

Rilpivirine: May decrease the absorption of Didanosine. More specifically, simultaneous coadministration of these drugs creates a conflict between recommendations to administer with (rilpivirine) and without (didanosine) food. Didanosine may decrease the absorption of Rilpivirine. More specifically, simultaneous coadministration of these drugs creates a conflict between recommendations to administer with (rilpivirine) and without (didanosine) food. Management: Administer didanosine on an empty stomach at least 2 hours before or 4 hours after rilpivirine, due to the requirement that rilpivirine be administered with food. Consider therapy modification

Stavudine: May enhance the adverse/toxic effect of Didanosine. Lactic acidosis (possibly fatal) is of particular concern. Management: Use extreme caution and monitor for lactic acidosis with concomitant stavudine and didanosine therapy. Avoid use of stavudine and didanosine (in combination or alone) with hydroxyurea due to increased risk of serious toxicity. Consider therapy modification

Tenofovir Disoproxil Fumarate: May diminish the therapeutic effect of Didanosine. Tenofovir Disoproxil Fumarate may increase the serum concentration of Didanosine. Management: Avoid concomitant treatment with tenofovir disoproxil fumarate and didanosine. Consider altering even existing, stable treatment to avoid this combination. Avoid combination

Tipranavir: May decrease the serum concentration of Didanosine. Management: It is recommended that didanosine be administered at least 2 hours apart from tipranavir in order to minimize any potential dosage form-related interaction. Consider therapy modification


Monitoring Parameters

Serum potassium, uric acid, creatinine; hemoglobin, CBC with neutrophil and platelet count, CD4 cells; viral load; liver function tests, serum bilirubin, albumin, INR, amylase; weight gain; perform dilated retinal exam every 6 months, ultrasonography (if portal hypertension suspected)


Adverse Reactions


As reported in monotherapy studies; risk of toxicity may increase when combined with other agents.

>10%:

Central nervous system: Peripheral neuropathy (17% to 20%)

Endocrine & metabolic: Increased amylase (15% to 17%)

Gastrointestinal: Diarrhea (19% to 28%), abdominal pain (7% to 13%)

1% to 10%:

Dermatologic: Pruritus ( ≤7% to 9%), skin rash ( ≤7% to 9%)

Endocrine & metabolic: Increased uric acid (2% to 3%)

Gastrointestinal: Pancreatitis (1% to 7%; dose-dependent; >65 years of age: 10%; younger patients: 5%)

Hepatic: Increased serum AST (7% to 9%), increased serum ALT (6% to 9%), increased serum alkaline phosphatase (1% to 4%)

<1% (Limited to important or life-threatening: Alopecia, anaphylactoid reaction, anemia, anorexia, arthralgia, chills, diabetes mellitus, dyspepsia, fever, flatulence, granulocytopenia, hepatic failure, hepatitis, hepatomegaly, hyperglycemia, hypersensitivity reaction, hypoglycemia, immune reconstitution syndrome, lactic acidosis, leukopenia, lipodystrophy, liver steatosis, myalgia, myopathy, optic neuritis, pain, parotid gland enlargement, portal hypertension (noncirrhotic), renal insufficiency (acute), retinal pigment changes (depigmentation), rhabdomyolysis, sialadenitis, Stevens-Johnson syndrome, symptomatic hyperlactatemia, thrombocytopenia, weakness, xerophthalmia, xerostomia


Warnings/Precautions


Special Populations: Renal Function Impairment

Clearance decreased as the CrCl decreased.


Special Populations: Hepatic Function Impairment

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


Warnings/Precautions

Concerns related to adverse effects:

- Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

- Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves ' disease, polymyositis, Guillain-Barre syndrome) later in therapy; further evaluation and treatment may be required.

- Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported, including fatal cases, with nucleoside analogues, alone or in combination, including didanosine and other antiretrovirals. Risk may be increased with female gender, obesity, or prolonged exposure. 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. Use caution when administering to patients with known risk factors for liver disease. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).

- Noncirrhotic portal hypertension: Patients may develop noncirrhotic portal hypertension within months to years of starting didanosine therapy. Signs may include elevated liver enzymes, esophageal varices, hematemesis, ascites, and splenomegaly. Noncirrhotic portal hypertension may lead to liver failure and/or death. Discontinue use in patients with evidence of this condition.

- Ocular effects: Retinal changes (including retinal depigmentation) and optic neuritis have been reported in adults and children using didanosine; patients should undergo retinal examination periodically.

- Pancreatitis: [U.S. Boxed Warning]: Pancreatitis (fatal and nonfatal) has been reported alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. Suspend use in patients with suspected pancreatitis and discontinue in patients with confirmed pancreatitis; frequency is dose related. In patients with risk factors for pancreatitis, use with extreme caution and only if clearly indicated. Patients with advanced HIV-1 infection, especially the elderly, are at increased risk and should be followed closely. Patients with renal impairment may be at greater risk for pancreatitis if treated without dose adjustment.

- Peripheral neuropathy: Peripheral neuropathy (numbness, tingling or pain in the hands or feet) has been reported, more frequently in patients with advanced HIV disease, in patients with a history of neuropathy or in patients being treated with a neurotoxic drug (eg, stavudine). Discontinue therapy if neuropathy occurs.

Disease-related concerns:

- Hepatic impairment: Use with caution in patients with hepatic impairment; safety and efficacy have not been established in patients with significant hepatic disease. Patients on combination antiretroviral therapy with hepatic impairment may be at increased risk of potentially severe and fatal hepatic toxicity; consider interruption or discontinuation of therapy if hepatic impairment worsens.

- Renal impairment: Use with caution in patients with renal impairment; dose reduction recommended for CrCl <60 mL/minute.

Concurrent drug therapy issues:

- Hydroxyurea and stavudine: Fatal cases of hepatotoxicity/lactic acidosis and/or severe peripheral neuropathy have been reported in HIV patients treated with didanosine with hydroxyurea and stavudine; avoid use with hydroxyurea or stavudine.

- Tenofovir: Combined use may be associated with increased didanosine toxicity (eg, lactic acidosis, pancreatitis), immunologic nonresponse or CD4 cell decline despite viral suppression, early virologic failure and rapid resistance development; combined use is not recommended (HHS [adult], 2015); manufacturer labeling recommends a didanosine dose reduction if combination is used.

- Drug-drug interactions: Additional potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

- Delayed release capsules: Didanosine delayed release capsules are indicated for once-daily use.

- Powder for oral solution: Didanosine powder for oral solution is recommended for use in a twice daily regimen, as there is more efficacy evidence with twice daily administration.

Special populations:

Pediatric: Dosing recommendations for didanosine powder for oral solution in patients younger than 2 weeks cannot be made because the pharmacokinetics of didanosine in these infants are too variable to determine an appropriate dose. Delayed-release capsules may be used in pediatric patients who weigh at least 20 kg.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Didanosine has a low to moderate level of transfer across the human placenta. Based on data from the Antiretroviral Pregnancy Registry, an increased rate of birth defects has been observed following maternal use of didanosine during the first trimester and later during pregnancy; no pattern of defects has been observed and clinical relevance is uncertain. Cases of lactic acidosis/hepatic steatosis syndrome related to mitochondrial toxicity have been reported with use of nucleoside analogues. In addition, these adverse events are similar to other rare but life-threatening syndromes which occur during pregnancy (eg, HELLP syndrome). In general nucleoside reverse transcriptase inhibitors are well tolerated and the benefits of use generally outweigh potential risk. However, due to reports of potentially fatal lactic acidosis, didanosine and stavudine should not be used in combination during pregnancy. The HHS Perinatal HIV Guidelines recommend didanosine to be used only in special circumstances during pregnancy; not recommended for initial therapy in antiretroviral-naive pregnant women due to toxicity. Pharmacokinetics are not significantly altered during pregnancy; dose adjustments of didanosine are not needed.

Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women. The goal of therapy is to keep the viral load below the limit of detection and prevent perinatal transmission. Therapy must be individualized. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, contraindications for use in pregnancy are not present, and the regimen is well tolerated. For HIV infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s). When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should be considered as soon as possible after diagnosis to reduce the risk of perinatal transmission. If antiretroviral drug-resistance testing is done, treatment may be started prior to obtaining results, then adjusted accordingly. Monitoring during pregnancy is more frequent than in non-pregnant adults. If cART must be interrupted for <24 hours, stop then restart all medications simultaneously in order to decrease the chance of developing resistance. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.

HIV infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.

Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2016).


Actions


Pharmacology

Didanosine, a purine nucleoside (adenosine) analog and the deamination product of dideoxyadenosine (ddA), inhibits HIV replication in vitro in both T cells and monocytes. Didanosine is converted within the cell to the mono-, di-, and triphosphates of ddA. These ddA triphosphates act as substrate and inhibitor of HIV reverse transcriptase substrate and inhibitor of HIV reverse transcriptase thereby blocking viral DNA synthesis and suppressing HIV replication.


Absorption

Subject to degradation by acidic pH of stomach; some formulations are buffered to resist acidic pH; ≤55% reduction in peak plasma concentration is observed in presence of food. Delayed release capsules contain enteric-coated beadlets which dissolve in the small intestine.


Distribution

Extensive intracellular distribution

CSF/plasma ratio: Infants 8 months to Adolescents 19 years: 46% (range: 12% to 85%); Adults: 21%

Vd(apparent):

Age-based:

Infants 8 months to Adolescents 19 years: 28 ‚ ± 15 L/m2

Adults: 43.7 ‚ ± 8.9 L/m2

Weight-based:

Children 20 kg to <25 kg: 98 ‚ ± 30 L

Children 25 kg to <60 kg: 155 ‚ ± 55 L

Children ≥60 kg: 363 ‚ ± 138 L

Adults ≥60 kg: 308 ‚ ± 164 L


Metabolism

Has not been evaluated in humans; studies conducted in dogs, show extensive metabolism with allantoin, hypoxanthine, xanthine, and uric acid being the major metabolites found in urine


Excretion

Unchanged drug excreted in urine

Infants 8 months to Adolescents 19 years: 18% ‚ ± 10%

Adults: 18% ‚ ± 8%


Time to Peak

Delayed release capsules: 2 hours; Powder for suspension: 0.25 to 1.5 hours


Half-Life Elimination

Plasma:

Newborns (1 day old): 2 ‚ ± 0.7 hours

Infants 2 weeks to 4 months: 1.2 ‚ ± 0.3 hours

Infants 8 months to Adolescents 19 years: 0.8 ‚ ± 0.3 hours

Adults with normal renal function: 1.5 ‚ ± 0.4 hours

Intracellular: Adults: 25 to 40 hours

Elimination: Increased as CrCl decreased

Children 20 kg to <25 kg: 0.75 ‚ ± 0.13 hours

Children 25 kg to <60 kg: 0.92 ‚ ± 0.09 hours

Children ≥60 kg: 1.26 ‚ ± 0.19 hours

Adults ≥60 kg: 1.19 ‚ ± 0.21 hours; 2 ‚ ± 0.3 hours (renal impairment [CrCl <30 mL/minute]); 4.1 ‚ ± 1.2 hours (dialysis)


Protein Binding

<5%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience headache, abdominal pain, nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of too much lactic acid in the blood (lactic acidosis; fast breathing, fast heartbeat, abnormal heartbeat, vomiting, drowsiness, shortness of breath, feeling very tired or weak, severe dizziness, feeling cold, or muscle pain or cramps), signs of a pancreas problem (pancreatitis; severe abdominal pain, severe back pain, severe nausea, vomiting), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe dizziness, passing out, burning or numbness feeling, bruising, bleeding, vision changes, change in body fat, or signs of infection (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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