RESTINN CAPSULES (EACH HARD GELATIN CAPSULE CONTAINS ESSENTIAL PHOSPHOLIPIDS /MELATONIN/INOSITOL)

Adverse effects

• Arthralgia
• Infection
• Dizziness
• Dry mouth
• Gastrointestinal discomfort
• Headaches
• Nausea
• Altered mood
• Night sweats
• Skin reactions
• Aggression
• Depression
• Disorientation
• Weight gain
• Electrolyte imbalance

Interactions

• Fluvoxamine: Severe (increases exposure)
• Givosiran: Moderate (increases exposure)
• Phenytoin: Unknown (decreases exposure)
• Axitinib: Unknown (increases exposure)
• Ritonavir: Unknown (decreases exposure)
• Leflunomide: Unknown (decreases exposure)
• Mexiletine: Unknown (increases exposure)
• Osilodrostat: Unknown (increases exposure)
• Rucaparib: Unknown (increases exposure)
• Teriflunomide: Unknown (decreases exposure)

Precautions

• Use with caution in hepatic impairment
• Use with caution in renal impairment
• Drowsiness may persist into the next day, affecting performance of skilled tasks such as driving

Pregnancy

No information available-avoid.

Breast-feeding

Present in milk-avoid.

Storage

Store in a cool, dry place away from light.

Formulations

• Modified-release tablets (Circadin®, Slenyto®)
• Immediate-release tablets (Adaflex®, Ceyesto®, Syncrodin®)
• Hard capsules
• Oral solution

Indications

• Infectious diseases
• Pain management
• Chronic diseases management
• Acute conditions
• Preventive care

Dosage

Children: Refer to specific guidelines for individual essential medicines as dosing varies widely.

Adults: Refer to specific guidelines for individual essential medicines as dosing varies widely.

Mechanism of action

The mechanisms of action for essential medicines vary widely depending on the specific drug. Generally, they can include a variety of pathways, such as inhibition of bacterial cell wall synthesis, modulation of neurotransmitter systems, or alteration of metabolic pathways. This diversity allows them to address a wide range of conditions effectively.

Pharmacodynamics

Pharmacodynamics of essential medicines involve their effects on the body and the mechanisms through which they exert therapeutic effects. This can include interactions with specific receptors, enzymes, or other molecular targets that result in a physiological response. For example, antibiotics can inhibit bacterial growth, while analgesics may modulate pain pathways in the central nervous system.

Pharmacokinetics

Pharmacokinetics of essential medicines vary significantly based on the specific drug and can include absorption, distribution, metabolism, and excretion (ADME). Generally, pharmacokinetic parameters such as bioavailability, volume of distribution, half-life, and clearance are critical in determining the dosing regimens and effectiveness of these medicines.

Pregnancy

Consult a healthcare provider before use. Safety during pregnancy has not been well established.

Breast-feeding

Consult a healthcare provider before use. Safety during breastfeeding has not been well established.

Storage

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

Indications

• Polycystic ovary syndrome (PCOS)
• Generalized anxiety disorder
• Depression
• Obsessive-compulsive disorder
• Insulin resistance

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines for paediatric patients.

Adults: Refer to the BNF for specific dosing recommendations, as doses may vary based on the condition being treated.

Mechanism of action

Inositol functions primarily as a precursor for the synthesis of phosphoinositides, which are key components of cell membranes. These phosphoinositides are involved in various intracellular signaling pathways, particularly those mediated by G-protein coupled receptors. Inositol also influences the action of neurotransmitters such as serotonin and has been shown to enhance insulin sensitivity and glucose metabolism.

Pharmacodynamics

Inositol has been observed to have mood-stabilizing effects and may improve insulin sensitivity. Its role in cell signaling impacts various physiological processes, including cellular communication and metabolic regulation. The therapeutic effects of inositol in psychiatric conditions may be attributed to its ability to modulate neurotransmitter systems, particularly involving serotonin and dopamine.

Pharmacokinetics

Inositol is well-absorbed from the gastrointestinal tract, with peak plasma levels occurring within 1 to 2 hours after ingestion. It is distributed throughout the body and can cross the blood-brain barrier. Inositol is predominantly excreted in the urine, with a half-life that varies based on dosage and individual metabolism. Metabolism occurs primarily through dephosphorylation to form various inositol phosphates.

Pregnancy

Inositol is generally considered safe during pregnancy but should be used under medical supervision.

Breast-feeding

Inositol is likely safe during breastfeeding, but consult a healthcare provider for specific recommendations.

Storage

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

Formulations

• Powder
• Capsules

Indications

• Lipid replacement therapy
• Nutritional supplementation
• Support in liver disease
• Support in skin conditions

Dosage

Children: Dosing for children should be determined by a healthcare provider, based on individual clinical circumstances and specific formulations.

Adults: Dosing of phospholipids varies widely based on specific formulations and clinical indications. It is essential to refer to specific product guidelines or consult a healthcare professional for appropriate dosing.

Mechanism of action

Phospholipids serve as structural components of cell membranes, forming lipid bilayers that provide a barrier to the passage of ions and polar molecules. They also participate in cell signaling pathways, where they can be hydrolyzed to produce second messengers like diacylglycerol and inositol triphosphate, which are involved in various cellular processes.

Pharmacodynamics

Phospholipids influence membrane fluidity and permeability, affecting the function of membrane proteins and the interaction of cells with their environment. They also play a crucial role in the formation of lipid rafts, which are microdomains in the membrane that organize signaling molecules and facilitate cellular communication.

Pharmacokinetics

Phospholipids are absorbed from the gastrointestinal tract and are distributed throughout the body in various tissues. They undergo metabolic processes involving enzymatic hydrolysis and re-esterification, leading to the production of other lipids and bioactive molecules. The half-life and elimination pathways can vary depending on the specific type of phospholipid and its physiological role.

Pregnancy

Phospholipids are generally considered safe during pregnancy, as they are naturally occurring components of cell membranes and are involved in various physiological processes. However, specific formulations should be evaluated for safety.

Breast-feeding

Phospholipids are found in human milk and are deemed safe during breastfeeding. They play a role in infant nutrition and development.

Storage

Phospholipids should be stored in a cool, dry place, away from light. Specific storage conditions may vary based on the formulation.

Formulations

• Phosphatidylcholine
• Phosphatidylethanolamine
• Phosphatidylserine
• Phosphatidylinositol

Mechanism of action

Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate. By binding to melatonin receptors 1 and 2, the downstream signallling cascades have various effects in the body. The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. There are two subtypes of the receptor in humans, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types.The binding of the agonists to the receptors has been investigated for over two decades or since 1986. It is somewhat known, but still not fully understood. When melatonin receptor agonists bind to and activate their receptors it causes numerous physiological processes. MT1 receptors are expressed in many regions of the central nervous system (CNS): suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantia nigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens. MT1 is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT2 receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes. The binding of melatonin to melatonin receptors activates a few signaling pathways. MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell. The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP.[4] As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell. Melatonin is implicated in numerous physiological processes, including circadian rhythms, stress, and reproduction, many of which are mediated by the hypothalamus and pituitary. The physiological actions of melatonin are mainly mediated by melatonin receptors. /The authors/ describe the distribution of the melatonin receptor MT1 in the human hypothalamus and pituitary by immunocytochemistry. MT1 immunoreactivity showed a widespread pattern in the hypothalamus. In addition to the area of the suprachiasmatic nucleus (SCN), a number of novel sites, including the paraventricular nucleus (PVN), periventricular nucleus, supraoptic nucleus (SON), sexually dimorphic nucleus, the diagonal band of Broca, the nucleus basalis of Meynert, infundibular nucleus, ventromedial and dorsomedial nucleus, tuberomamillary nucleus, mamillary body, and paraventricular thalamic nucleus were observed to have neuronal MT1 receptor expression. No staining was observed in the nucleus tuberalis lateralis and bed nucleus of the stria terminalis. The MT1 receptor was colocalized with some vasopressin (AVP) neurons in the SCN, colocalized with some parvocellular and magnocellular AVP and oxytocine (OXT) neurons in the PVN and SON, and colocalized with some parvocellular corticotropin-releasing hormone (CRH) neurons in the PVN. In the pituitary, strong MT1 expression was observed in the pars tuberalis, while a weak staining was found in the posterior and ant

Pharmacodynamics

Melatonin is a hormone normally produced in the pineal gland and released into the blood. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. It helps regulate sleep-wake cycles or the circadian rhythm. Production of melatonin is stimulated by darkness and inhibited by light. High levels of melatonin induce sleep and so consumption of the drug can be used to combat insomnia and jet lag. MT1 and MT2 receptors may be a target for the treatment of circadian and non circadian sleep disorders because of their differences in pharmacology and function within the SCN. SCN is responsible for maintaining the 24 hour cycle which regulates many different body functions ranging from sleep to immune functions