DIDANOSINE>250 250MG DELAYED RELEASE CAPSULES

Indications

• HIV infection
• HIV-1 infection (specialist use only)

Dosage

Children: Child 1–7 months: 50–100 mg/m2 twice daily. Child 6–11 years (body-weight 25 kg and above): 1 tablet once daily. Child 12–17 years (body-weight 35 kg and above): 1 tablet once daily

Adults: Refer to BNF for specific dosing guidelines for adults. Typically, the dose is determined based on individual clinical circumstances and concurrent medications.

Mechanism of action

Didanosine is converted intracellularly to dideoxyadenosine triphosphate (ddATP), which inhibits HIV reverse transcriptase competitively by mimicking natural dATP. It also acts as a chain terminator upon incorporation into viral DNA due to the lack of a 3'-OH group, preventing further DNA strand elongation and ultimately terminating viral DNA synthesis. This results in a virustatic effect against retroviruses, especially HIV.

Pharmacodynamics

Didanosine exhibits its antiviral effects by competing with natural nucleotides for incorporation into viral DNA, thereby inhibiting the activity of the reverse transcriptase enzyme. This mechanism is characteristic of nucleoside analogs, which disrupt the replication of HIV. Didanosine's efficacy is enhanced when used in combination with other antiretroviral therapies, and it has shown benefits in patients switching from long-term zidovudine (AZT) treatment.

Pharmacokinetics

Didanosine is absorbed through the gastrointestinal tract and is subject to intracellular phosphorylation to its active metabolite. It has a variable half-life and is primarily eliminated through renal mechanisms. The pharmacokinetics can be affected by factors such as food intake and concurrent use of antacids, which can alter its absorption profile.

Adverse effects

• arthralgia
• chills
• dry mouth
• fever
• flatulence
• gynaecomastia
• hepatic disorders
• pain
• peripheral neuropathy
• alopecia
• diabetes mellitus
• dry eye
• hyperglycaemia
• hypoglycaemia
• leucopenia
• myopathy
• optic neuritis
• retinal discoloration
• sialadenitis
• parotid gland enlargement
• lipoatrophy
• pancreatitis

Interactions

• abacavir
• lamivudine
• zidovudine
• elvitegravir with cobicistat
• emtricitabine
• tenofovir alafenamide

Precautions

• History of pancreatitis
• Use with caution in patients with hepatomegaly, hepatitis, or other risk factors for liver disease
• Monitor for toxicity in hepatic impairment
• Discontinue treatment if symptoms of hyperlactataemia, lactic acidosis, or rapid deterioration of liver function occur

Pregnancy

Data on the use of didanosine in pregnancy is limited; however, it is advisable to monitor for potential risks, as it may be associated with low exposure during the second and third trimesters.

Breast-feeding

It is not known if didanosine is excreted in human milk; caution is advised when administering to breastfeeding mothers.

Storage

Store at room temperature, away from light and moisture.

Formulations

• Didanosine 125 mg gastro-resistant capsules
• Didanosine 250 mg gastro-resistant capsules
• Didanosine 400 mg gastro-resistant capsules

Indications

• Chronic pain management
• Gastroesophageal reflux disease (GERD)
• Irritable bowel syndrome
• Attention-deficit hyperactivity disorder (ADHD) management
• Chronic respiratory conditions requiring bronchodilation

Dosage

Children: Refer to specific product labeling or clinical guidelines for paediatric dosing information.

Adults: Refer to specific product labeling or clinical guidelines for adult dosing information.

Mechanism of action

The mechanism of action varies depending on the specific drug formulation. Generally, delayed-release formulations are designed to dissolve at a specific site in the gastrointestinal tract, allowing for a slower absorption process. This can enhance the drug's therapeutic effects while minimizing side effects associated with peak plasma concentrations.

Pharmacodynamics

The pharmacodynamics of delayed-release medications involve the interaction between the drug and its target receptors or enzymes over a prolonged period. This can lead to sustained therapeutic effects, reduced frequency of dosing, and improved patient adherence to treatment regimens. The slow release mechanism also helps in maintaining more stable plasma drug concentrations, potentially reducing the occurrence of adverse effects.

Pharmacokinetics

Pharmacokinetics of delayed-release drugs typically include altered absorption rates due to the formulation's design. The onset of action may be delayed compared to immediate-release formulations. The distribution, metabolism, and excretion of the drug will depend on its chemical properties, but generally, the half-life may be extended due to prolonged absorption. Many delayed-release formulations utilize polymers or other excipients that control the release rate of the active ingredient.

Pregnancy

The safety of delayed-release formulations during pregnancy has not been well established. Consultation with a healthcare provider is recommended.

Breast-feeding

Caution is advised when using delayed-release medications while breastfeeding, as effects on the infant are unknown.

Storage

Store at room temperature, away from moisture and direct sunlight. Keep out of reach of children.

Indications

• Bacterial infections
• Infections caused by susceptible organisms
• Prophylaxis in certain surgical procedures

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age, weight, and condition.

Adults: Refer to the BNF for specific dosages based on the condition being treated, severity of infection, and patient factors.

Mechanism of action

Release exerts its effects by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. This mechanism is primarily mediated through the disruption of peptidoglycan cross-linking, which is essential for maintaining the structural integrity of bacterial cell walls.

Pharmacodynamics

The pharmacodynamics of Release involves its bactericidal action against a wide range of gram-positive and some gram-negative bacteria. The drug displays a time-dependent killing effect, meaning that its efficacy is related to the duration of exposure rather than the peak concentration achieved. Resistance to Release can develop through various mechanisms, including alterations in target sites or enzymatic degradation.

Pharmacokinetics

Release is absorbed and distributed throughout the body following administration. Peak plasma concentrations are typically achieved within a few hours. The drug is metabolized primarily in the liver, with metabolites excreted via the kidneys. The half-life of Release can vary depending on individual patient factors, including age, liver function, and concurrent medications.

Mechanism of action

Didanosine (ddI) is metabolized intracellularly by a series of cellular enzymes to its active moiety, dideoxyadenosine triphosphate (ddATP), which inhibits the HIV reverse transcriptase enzyme competitively by competing with natural dATP. It also acts as a chain terminator by its incorporation into viral DNA as the lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. The complete mechanism(s) of antiviral activity of didanosine has not been fully elucidated. Following conversion to a pharmacologically active metabolite, didanosine apparently inhibits replication of retroviruses, including human immunodeficiency virus, by interfering with viral RNA directed DNA polymerase (reverse transcriptase). The drug, there exerts a virustatic effect against retroviruses by acting as a reverse transcriptase inhibitor. Like other nucleoside reverse transcriptase inhibitors (eg, abacavir, lamivudine, stavudine, zalcitabine, zidovudine) and other nucleoside antiviral agents (eg, acyclovir, ganciclovir, ribavirin), the antiviral activity of didanosine appears to depend on intracellular conversion of the drug to a 5'-triphosphate metabolite; thus, dideoxyadenosine-5'-triphosphate and not unchanged didanosine appears to be the pharmacologically active form of the drug. Substantial differences exist in the rates at which human cells phosphorylate various nucleoside analog antiviral agents and in the enzymatic pathways involved. Dideoxyadenosine-5'-triphosphate can bind to inhibit some mammalian cellular DNA polymerases, particularly beta- and gamma-polymerases, in vitro. However, dideoxyadenosine-5'-triphosphate and other dideoxynucleoside triphosphate appear to have much greater affinity for viral RNA directed DNA polymerase than for mammalian DNA polymerases, particularly mammalian DNA alpha-polymerase, a DNA enzyme essential for cell division and cellular DNA repair. This differential sensitivity of mammalian and viral DNA polymerases to dideoxynucleotide triphosphates may account, in part, for some of the antiviral selectivity of these drugs in cells that can phosphorylate them. However, inhibition of beta- and gamma-polymerases by these drugs may account to some extent, for the toxic effects associated with didanosine and other dideoxynucelosides in humans.

Pharmacodynamics

Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Didanosine is a hypoxanthine attached to the sugar ring, unlike other nucleoside analogues. Didanosine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. Didanosine is effective against HIV, and usually used in combination with other antiviral therapy. Switching from long term AZT treatment to didanosine has been shown to be beneficial. Didanosine has weak acid stability and therefore, it is often combined with an antacid.