INNOVAX-ND-IBD

Indications

• Multiple sclerosis
• Psoriasis (under expert supervision)

Dosage

Children: There is limited evidence regarding the use of dimethyl fumarate in pediatric populations. For pediatric dosing

Adults: The dosing regimen for adults is typically initiated at a lower dose, gradually increased based on tolerance and clinical response. For specific dosing information, please refer to the BNF.

Mechanism of action

The mechanism of action of dimethyl fumarate involves its conversion to monomethyl fumarate (MMF). MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which is activated in response to oxidative stress, and suppresses pro-inflammatory gene expression through the inhibition of nuclear factor kappa B. Additionally, MMF acts as a nicotinic acid receptor agonist, influencing immune cell composition and function, leading to a reduction in central nervous system infiltration and a shift from a pro-inflammatory to an anti-inflammatory immune phenotype.

Pharmacodynamics

Dimethyl fumarate exhibits anti-inflammatory and cytoprotective effects, which are particularly relevant in the context of multiple sclerosis. Although its precise physiological effects are not fully understood, it has been associated with the modulation of immune responses, potentially lowering the risk of relapse in multiple sclerosis patients. However, treatment with dimethyl fumarate can lead to serious adverse effects, including progressive multifocal leukoencephalopathy (PML), opportunistic infections, and severe lymphopenia.

Pharmacokinetics

Dimethyl fumarate is rapidly absorbed after oral administration, with peak plasma concentrations reached within hours. The drug is extensively metabolized to its active form, monomethyl fumarate, which is primarily eliminated via renal excretion. The pharmacokinetics may be influenced by factors such as liver function and concurrent medications. Monitoring of lymphocyte counts is recommended during treatment due to the risk of lymphopenia.

Contra-indications

• Severe lymphopenia (lymphocyte count below 0.5 x 10^9/litre)
• Active infection
• Severe active gastro-intestinal disease

Adverse effects

• Progressive multifocal leukoencephalopathy (PML)
• Lymphopenia
• Serious opportunistic infections
• Liver injury
• Anaphylaxis
• Angioedema
• Decreased leukocyte count
• Constipation
• Diarrhea
• Feeling hot
• Gastrointestinal discomfort
• Fatigue
• Eosinophilia

Interactions

• Live vaccines (unknown interaction, increases risk of generalized infection, possibly life-threatening)

Precautions

• Monitor lymphocyte counts at least every 3 months during treatment
• Re-evaluate treatment in patients with sustained moderate reductions of absolute lymphocyte counts (between 0.5 and 0.8 x 10^9/litre) for longer than 6 months
• Patients should be vigilant for new or worsening neurological or psychiatric symptoms

Pregnancy

There are limited data on the use of dimethyl fumarate in pregnancy. Caution is advised.

Breast-feeding

It is not known whether dimethyl fumarate is excreted in human milk. Caution is advised.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Dimethyl fumarate 120 mg and 240 mg delayed-release capsules

Indications

• Diabetes mellitus
• Hypoglycemia
• Certain immunodeficiencies
• Replacement therapy for hormone deficiencies

Dosage

Children: Refer to the specific product guidelines for dosing, as it varies widely based on the type of bovine-derived treatment.

Adults: Refer to the specific product guidelines for dosing, as it varies widely based on the type of bovine-derived treatment.

Mechanism of action

Bovine-derived products, such as insulin from bovine pancreas, function by mimicking the action of human hormones or proteins in the body. For example, insulin facilitates glucose uptake by cells, thereby lowering blood glucose levels in diabetic patients. The mechanism of action is largely dependent on the specific bovine product in question.

Pharmacodynamics

The pharmacodynamics vary widely depending on the specific bovine product. For insulin, the pharmacodynamics involve promoting the transport of glucose into cells, inhibiting hepatic glucose production, and enhancing lipid storage. Other bovine-derived products may have different effects based on their biological functions.

Pharmacokinetics

Pharmacokinetics also depend on the specific bovine product. For bovine insulin, absorption occurs rapidly after subcutaneous administration, with a peak effect typically seen within a few hours. The half-life can vary; for example, regular insulin has a short half-life, while long-acting formulations can provide sustained effects. Distribution and elimination will also depend on the specific product and formulation.

Pregnancy

There is limited data on the use of bovine-derived products during pregnancy. Caution is advised.

Breast-feeding

Limited data available; consult healthcare provider before use.

Storage

Store in a cool, dry place away from direct sunlight. Specific storage conditions may vary based on the formulation.

Indications

• Relapsing forms of multiple sclerosis
• Multiple sclerosis exacerbation

Dosage

Children: Refer to the BNF for Children for specific dosage recommendations for paediatric patients.

Adults: Refer to the BNF for specific dosage recommendations for adults.

Mechanism of action

Dimethyl fumarate is thought to activate the Nrf2 pathway, which leads to the induction of antioxidant proteins and a subsequent reduction in oxidative stress. This activation may also promote an anti-inflammatory response and modulate immune system activity, contributing to its beneficial effects in conditions such as multiple sclerosis.

Pharmacodynamics

Dimethyl fumarate exhibits immunomodulatory properties, influencing T-cell activation and promoting a shift from pro-inflammatory to anti-inflammatory immune responses. This modulation can help reduce the inflammatory processes associated with autoimmune diseases like multiple sclerosis. Additionally, the drug is associated with increased production of neuroprotective factors and a decrease in neuroinflammation.

Pharmacokinetics

Dimethyl fumarate is rapidly absorbed after oral administration, with peak plasma concentrations occurring within a few hours. It undergoes extensive first-pass metabolism, primarily converting to its active metabolite, monomethyl fumarate. The elimination half-life is approximately 30 minutes to 2 hours. Dimethyl fumarate and its metabolites are primarily excreted in the urine. Its pharmacokinetics may be influenced by food intake, with higher bioavailability observed when taken with meals.

Interactions

• live vaccines + dimethylfumarate: Unknown (increases risk of generalised infection (possibly life-threatening))

Indications

• Herpes Simplex Virus infection
• Genital herpes
• Cold sores
• Varicella (chickenpox)
• Herpes Zoster (shingles)
• Prevention of herpes virus reactivation in immunocompromised patients

Dosage

Adults: Refer to the BNF for specific dosing recommendations for adults

Mechanism of action

Herpesvirus antiviral medications, such as acyclovir and valacyclovir, primarily inhibit viral DNA synthesis. They are nucleoside analogs that get incorporated into the growing viral DNA chain, leading to premature termination of DNA synthesis. This action is selective for infected cells, as the drugs are activated by viral thymidine kinase, which is present in infected cells but absent in uninfected cells.

Pharmacodynamics

The pharmacodynamic profile of herpesvirus antivirals shows that they are more effective when administered early in the course of the infection. Acyclovir exhibits a higher affinity for viral DNA polymerase than for the host cell's enzymes, which reduces toxicity to human cells. The efficacy of these medications is related to the degree of viral replication; higher viral loads may require higher doses or more frequent administration.

Pharmacokinetics

Acyclovir is well absorbed after oral administration, with a bioavailability of approximately 15-30%. It is widely distributed in body fluids and tissues, including the central nervous system. It undergoes renal excretion, primarily as unchanged drug, necessitating dosage adjustment in patients with renal impairment. The half-life of acyclovir ranges from 2.5 to 3 hours in healthy adults, but this can be prolonged in cases of renal dysfunction. Valacyclovir, a prodrug of acyclovir, has improved bioavailability of approximately 54% and is converted to acyclovir in the body.

Contra-indications

• Hypersensitivity to acyclovir or any of its components
• Severe renal impairment

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Rash
• Renal toxicity
• Neurotoxicity (in cases of rapid infusion or dehydration)

Interactions

• Probenecid may reduce renal clearance of acyclovir
• Other nephrotoxic agents may increase the risk of renal impairment
• Zidovudine may increase the risk of hematological toxicity

Precautions

• Monitor renal function during treatment, especially in patients with pre-existing renal disease
• Hydration is important to prevent crystallization in the kidneys
• Use caution in patients with neurological conditions

Pregnancy

Acyclovir is classified as a category B drug. Animal studies have not demonstrated a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women.

Breast-feeding

Acyclovir is excreted in breast milk in small amounts. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Oral tablets
• Topical cream
• Intravenous injection
• Oral suspension

Indications

• Measles
• Mumps
• Rubella
• Varicella (chickenpox)
• Yellow fever
• Rotavirus
• Intranasal influenza

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and vaccine type.

Adults: Refer to specific product guidelines for dosing information, as it can vary by vaccine type and brand.

Mechanism of action

Live vaccines work by introducing a weakened or attenuated form of a pathogen into the body. This stimulates the immune system to recognize and respond to the pathogen, leading to the production of antibodies and memory cells that provide long-term protection against future infections by the same pathogen.

Pharmacodynamics

The pharmacodynamics of live vaccines involve the activation of both humoral and cellular immunity. Following vaccination, the immune system generates a robust response, including the production of specific antibodies and the activation of T cells that can recognize and eliminate infected cells. This dual action helps establish long-term immunity.

Pharmacokinetics

The pharmacokinetics of live vaccines vary depending on the specific vaccine. Generally, the vaccine is administered via injection, allowing the live attenuated organisms to enter the bloodstream. The immune response typically begins within days and can last for years, depending on the vaccine. Live vaccines are usually stored under refrigeration to maintain their viability, and they should be administered within their expiration dates.

Interactions

• livevaccines + abrocitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + baricitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + filgotinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + dexrazoxane: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + iron chelators: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + ozanimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + ponesimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + siponimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + upadacitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + diroximelfumarate: Moderate (increases risk of generalised infection (possibly life-threatening))

Dosage

Children: Refer to specific product guidelines as dosage will depend on the type of medium and its intended application.

Adults: Refer to specific product guidelines as dosage will depend on the type of medium and its intended application.

Mechanism of action

The mechanism of action for a medium can vary greatly depending on the specific medium being referenced. Generally, media serve to maintain the stability and viability of cells or organisms during culture, enabling metabolic processes to occur. For instance, nutrient media provide essential nutrients, while selective media may inhibit the growth of certain organisms while promoting others.

Pharmacodynamics

Pharmacodynamics is largely dependent on the type of medium used and its components. In tissue cultures, the medium can influence cell growth, differentiation, and physiological responses. The interactions of cells with their environment are critical for cellular signaling and function.

Pharmacokinetics

Pharmacokinetics is not typically applicable to media in the same way it is for active drugs. However, the absorption and distribution of substances within a medium can affect how well the active ingredients are delivered or how organisms interact with the medium. Factors such as pH, osmolarity, and nutrient concentration can all influence these processes.

Pregnancy

Consult a healthcare provider before use, as the safety of medium in pregnancy has not been established.

Breast-feeding

Consult a healthcare provider before use, as it is unknown whether medium passes into breast milk.

Storage

Store in a cool, dry place, away from direct sunlight and moisture.

Indications

• Diagnostic blood tests
• Assessment of organ function
• Evaluation of electrolyte balance
• Monitoring of therapeutic drug levels
• Detection of antibodies or infectious agents

Dosage

Children: Dosage is not applicable as serum is a biological fluid used for diagnostic purposes and not an administered drug.

Adults: Dosage is not applicable as serum is a biological fluid used for diagnostic purposes and not an administered drug.

Mechanism of action

Serum itself does not have a specific mechanism of action as it is a biological fluid. However, its components, particularly proteins such as albumin and immunoglobulins, contribute to homeostasis, transport, and immune response. Albumin helps in maintaining oncotic pressure and transporting various substances, while immunoglobulins play a vital role in the immune response.

Pharmacodynamics

The pharmacodynamics of serum are closely related to its composition. The proteins in serum, including enzymes, hormones, and antibodies, exert various physiological effects. For example, serum albumin helps maintain blood volume and pressure, while globulins are involved in immune function. Changes in serum composition can affect the pharmacodynamics of drugs, influencing their distribution, metabolism, and elimination.

Pharmacokinetics

Serum does not follow a traditional pharmacokinetic profile, as it is a complex mixture rather than a single drug. However, the elimination and distribution of substances within the serum can be influenced by factors such as protein binding, blood flow, and the physiological state of the individual. The half-life of any drugs or substances present in serum will depend on their specific characteristics and interactions with serum components.

Adverse effects

• Allergic reactions
• Infection at the injection site
• Fever
• Rash
• Joint pain

Precautions

• Use with caution in individuals with a history of allergic reactions
• Monitor for signs of infection
• Assess for any history of autoimmune conditions

Pregnancy

Consult healthcare provider. Safety in pregnancy is not well established.

Breast-feeding

Consult healthcare provider. Limited information is available regarding excretion in breast milk.

Storage

Store at 2 to 8 degrees Celsius. Do not freeze. Protect from light.

Formulations

• Intravenous solution
• Subcutaneous injection

Indications

• Bacterial infections
• Viral infections
• Epidemiological studies
• Antibiotic resistance monitoring

Dosage

Children: Refer to specific antimicrobial treatment guidelines based on the strain identified and the infection site.

Adults: Refer to specific antimicrobial treatment guidelines based on the strain identified and the infection site.

Mechanism of action

The mechanism of action for a strain depends on the type of microorganism it represents. For pathogenic bacteria, the strain may produce toxins, evade the host's immune response, or possess resistance mechanisms that allow it to survive in the presence of antibiotics. For viruses, strains may exhibit mutations that alter their ability to infect host cells or evade antiviral therapies.

Pharmacodynamics

Pharmacodynamics in the context of strains involves the interaction between the strain and the host's immune system, as well as the effects of specific antimicrobial agents on the strain. These interactions can influence the efficacy of treatments and the development of resistance.

Pharmacokinetics

Pharmacokinetics is not directly applicable to strains themselves but rather to the drugs used to treat infections caused by specific strains. Factors such as absorption, distribution, metabolism, and excretion of antimicrobial agents can vary depending on the strain's characteristics and the site of infection.

Pregnancy

There is limited information on the safety of strain in pregnancy. It is advisable to consult healthcare professionals for guidance.

Breast-feeding

Safety during breastfeeding is not well established. It is recommended to seek medical advice before use.

Storage

Store in a cool, dry place, away from direct sunlight and moisture. Keep out of reach of children.

Indications

• Insecticide synergist
• Enhancement of insecticidal efficacy

Dosage

Children: Refer to specific product guidelines for paediatric dosing, as it varies based on formulation and intended use.

Adults: Refer to specific product guidelines for adult dosing, as it varies based on formulation and intended use.

Mechanism of action

Sulfoxide functions by inhibiting hepatic microsomal oxidase enzymes, which are involved in the detoxification of drugs and chemicals in the body. It acts as a competitive substrate for these enzymes, thereby increasing vulnerability to various toxic substances due to impaired detoxification processes.

Pharmacodynamics

The pharmacodynamics of sulfoxide involve its ability to modify the metabolism of other drugs and chemicals through enzyme inhibition. This can lead to increased systemic exposure to co-administered substances, affecting their efficacy and safety profiles.

Pharmacokinetics

The pharmacokinetics of sulfoxide, including its absorption, distribution, metabolism, and excretion, are not well-documented in humans. However, similar compounds suggest that it may undergo hepatic metabolism and could be subject to variations in individual responses based on enzyme activity.

Pregnancy

Use in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution during breastfeeding, as it is not known whether sulfoxide is excreted in human milk.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Indications

• High-quality protein source
• Nutritional support for muscle maintenance
• Source of B vitamins
• Source of selenium
• Source of zinc

Dosage

Children: Protein needs for children vary by age. It is recommended to consult specific dietary guidelines for children, which suggest that the intake of protein should be proportionate to their age, weight, and level of physical activity.

Adults: The recommended dietary allowance for protein varies, but generally, adults require approximately 46-56 grams of protein per day, which can be met through the consumption of turkey as part of a balanced diet.

Mechanism of action

Turkey meat contains proteins that are broken down into amino acids during digestion, which the body utilizes for various physiological functions, including muscle repair, hormone production, and immune function. The presence of tryptophan, an amino acid found in turkey, is known to affect serotonin levels in the brain, which may influence mood and sleep patterns.

Pharmacodynamics

Turkey is rich in amino acids, vitamins, and minerals, which can support overall health. The bioavailability of nutrients such as zinc and B vitamins from turkey contributes to various metabolic processes and functions, including energy production, immune response, and nervous system health. The consumption of turkey is associated with satiety and may impact dietary patterns due to its protein content.

Pharmacokinetics

Nutrient absorption from turkey occurs primarily in the gastrointestinal tract, where proteins are digested into amino acids, and vitamins and minerals are absorbed into the bloodstream. The rate of absorption may vary based on the method of cooking and individual digestive health. Protein metabolism involves hepatic processing, where amino acids are utilized or stored as needed by the body.

Pregnancy

Generally considered safe to consume during pregnancy, but should be cooked thoroughly to avoid foodborne illnesses.

Breast-feeding

Typically safe for breastfeeding mothers, but should be prepared properly to ensure safety for both mother and infant.

Storage

Store in a cool, dry place. Fresh turkey should be refrigerated and consumed within a few days or frozen for longer storage.

Mechanism of action

The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite, monomethyl fumarate (MMF). Both dimethyl fumarate and MMF up-regulate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate also suppresses pro-inflammatory genes through nuclear factor kappa B inhibition. Additionally, MMF acts as an agonist at the nicotinic acid receptor, but the relevance of this is unknown. It has been suggested that dimethyl fumarate exerts its immunomodulatory effects through changes in the composition and phenotype of immune cells. It reduces CNS infiltration and alters the composition of all lymphocyte subpopulations, especially for cytotoxic and effector T cells. This causes a shift from a mainly pro-inflammatory phenotype to an anti-inflammatory one. Dimethyl fumarate (DMF) is a fumaric acid ester that is used to treat psoriasis and multiple sclerosis. Recently, DMF was found to exhibit anti-tumor effects. However, the molecular mechanisms underlying these effects have not been elucidated. In this study, we investigated the mechanism of DMF-induced apoptosis in different human hematopoietic tumor cell lines. We found that DMF induced apoptosis in different human hematopoietic tumor cell lines but it did not affect the normal human B lymphocyte cell line RPMI 1788. We also observed a concurrent increase in caspase-3 activity and in the number of Annexin-V-positive cells. Furthermore, an examination of the survival signals, which are activated by apoptotic stimuli, revealed that DMF significantly inhibited nuclear factor-kB (NF-kB) p65 nuclear translocation. In addition, DMF suppressed B-cell lymphoma extra-large (Bcl-xL) and X-linked inhibitor of apoptosis (XIAP) expression whereas Bcl-2, survivin, Bcl-2-associated X protein (Bax), and Bim levels did not change. These results indicated that DMF induced apoptosis by suppressing NF-kB activation, and Bcl-xL and XIAP expression. These findings suggested that DMF might have potential as an anticancer agent that could be used in combination therapy with other anticancer drugs for the treatment of human hematopoietic tumors. Oxidative stress plays a crucial role in many neurodegenerative conditions such as Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's as well as Huntington's disease. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis (MS). Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic-progressive MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). ... In vitro, application of dimethylfumarate (DMF) leads to stabilization of Nrf2, activation of Nrf2-dependent transcriptional activity and abundant synthesis of detoxifying proteins. Furthermore, application of FAE involves direct modification of the inhibitor of Nrf2, Kelch-like ECH-associated protein 1. On cellular levels, the application of FAE enhances neuronal survival and protects astrocytes against oxidative stress. Increased levels of Nrf2 are detected in the central nervous system of DMF treated mice suffering from experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In EAE, DMF ameliorates the disease course and improves preservation of myelin, axons and neurons. Finally, Nrf2 is also up-regulated in the spinal cord of autopsy specimens from untreated patients with MS, probably as part of a naturally occurring anti-oxidative response. In summary, oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapies like FAE. Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegen

Pharmacodynamics

The physiological effects of dimethyl fumarate on the body are not well understood. It has anti-inflammatory and cytoprotective effects, likely involved in its actions in multiple sclerosis (MS) patients. Dimethyl fumarate does not cause clinically significant QT interval prolongation. However, cases of progressive multifocal leukoencephalopathy, serious opportunistic infections, lymphopenia and liver injury have been reported in MS patients treated with this drug. Dimethyl fumarate may also cause anaphylaxis and angioedema.

Mechanism of action

Piperonyl butoxide, like other methylenedioxybenzene synergists (eg, sesamex, sulfoxide, n-propyl isome, piperonyl cyclonene, etc), inhibits hepatic microsomal oxidase enzymes in lab rodents & by inference in man; it also inhibits a related group of enzymes in insects apparently by serving as a competitive substrate. Because these enzymes act to detoxify many drugs & other exogenous chemicals, a heavy exposure to one of these insecticidal synergists might make a person temporarily vulnerable to a variety of toxic insults that would normally be tolerated with ease.