RELSED: composition and presentation
RELSED is a solution of diazepam in microenemas for rectal administration. One 2.5 ml microenema contains either 5 mg or 10 mg of diazepam, and that is the only thing that depends on the pack. Everything else is identical, and the composition is worth a look: the excipients here are more numerous and count for more than in a tablet of the same diazepam.
| Component | How much | What it means |
| Benzyl alcohol | 37.5 mg in 2.5 ml | allergic reactions are possible; in newborns it is linked to the risk of gasping syndrome, a severe breathing disorder; children under 3 are not given the medicine for longer than a week because it accumulates |
| Ethanol | 12.4% v/v, up to 250 mg per microenema — as much as in 5.94 ml of beer or 2.48 ml of wine | harmful in alcohol dependence; taken into account in pregnant and breastfeeding women, in children, in liver disease and in epilepsy |
| Propylene glycol | 400 mg in 1 ml, that is 1000 mg per microenema | together with ethanol and other substrates of alcohol dehydrogenase it may cause adverse effects in children under 5; it crosses to the foetus and into milk; in kidney and liver disease medical supervision is needed |
| Sodium benzoate | 48.8 mg in 1 ml | may increase the risk of jaundice in newborns |
This list explains some of the restrictions that look surprisingly strict for so short a course: they follow not only from the diazepam but from the solvents it is dissolved in. That is why in newborns and in children in their first years of life the decision rests with the doctor rather than the parent, even when the medicine is already in the house.
How RELSED works
Diazepam belongs to the 1,4-benzodiazepines. It acts through the GABA-A receptor complex, which contains a binding site for benzodiazepines: the drug strengthens the binding of gamma-aminobutyric acid to that receptor. From there the chain is purely physical — chloride ions enter the neuron more readily, the cell hyperpolarises and its bioelectrical activity is damped down. The result is a strengthening of the inhibitory action of GABA in the central nervous system, and from it follow all four effects of diazepam: anxiolytic, hypnotic, anticonvulsant and skeletal muscle relaxant.
The microenema form was not chosen for convenience: it is meant for situations where fast action is needed while intravenous administration is difficult or undesirable — for instance in a child having seizures before the ambulance arrives. The rectum has a rich blood supply, the substance is absorbed quickly, and the procedure requires neither a syringe nor the skill of putting in a line.
Indications
The indications gather conditions united not by a diagnosis but by the need to suppress excess excitation at once. They are febrile convulsions, status epilepticus, eclampsia in pregnancy, anxiety attacks, states with increased muscle tone and tetanus. A separate entry covers premedication before various diagnostic and surgical procedures and sedation in the postoperative period.
The list is half paediatric and half adult: febrile convulsions are almost exclusively a childhood story, eclampsia is obstetric, and premedication concerns any age. All the indications share one thing: the medicine is used once, or for a few days, never as a course of treatment. That is precisely why the warnings state plainly that single microenemas are used for emergency administration and that in other cases the medicine is not used for longer than a few days.
Method of use and dosage
Children from 7 months of age are given up to 0.5 mg per kilogram of body weight; at 10–15 kg that is one 5 mg microenema and above 15 kg it is 10 mg, that is two 5 mg microenemas or one of 10 mg. If the convulsions do not stop, the dose is repeated after 10–15 minutes. Children at high risk of recurrent febrile convulsions are given it every 8 hours while the fever is above 38.5 °C. In adults with status epilepticus, eclampsia, anxiety attacks, states with increased muscle tone and tetanus, treatment starts with 5–10 mg and, if that is ineffective, the dose is repeated after about 10–15 minutes, with no more than 30 mg of diazepam in total. For premedication, 10–20 mg is given on the day before the procedure, and 5–10 mg both 30 to 60 minutes before anaesthesia and after the procedure. Elderly people and patients with renal, hepatic, circulatory or respiratory failure need smaller doses: treatment starts at 5 mg a day and is increased gradually, once tolerance has been confirmed.
The technique of administration is described step by step, and whether the dose ends up where it should depends on it. During administration and for a further 15 minutes the person should lie flat, face down, on the stomach. The cannula is lubricated with gel and opened by twisting its tip. It is inserted into the rectum in full; in small children, halfway. The reservoir is emptied by squeezing hard with thumb and forefinger, after which the cannula is withdrawn without releasing the squeeze — otherwise some of the solution is drawn back into the tube. For 24 hours afterwards one must not drive or operate machinery.
Contraindications
The medicine is not used in hypersensitivity to diazepam, to other benzodiazepines or to any excipient, nor in myasthenia, severe respiratory failure, sleep apnoea syndrome and severe liver failure, of which cholestatic jaundice is given as an example. The logic of the first bans is transparent: diazepam relaxes muscles and depresses the respiratory centre, and in myasthenia and apnoea that is exactly what must not be allowed. One microenema holds 19.5 mg of sodium, under one per cent of the WHO daily maximum, so it has no bearing on diet.
The last two entries work differently. Phobias and obsessions are on the list because benzodiazepines do not treat them, yet have time to create dependence. Monotherapy of depression, or of anxiety linked to depression, is forbidden for a graver reason: the drug lifts inhibition without altering the low mood, and that raises the risk of suicide attempts. The ban here follows not from toxicity but from the medicine standing in for the treatment that is actually needed.
Special warnings and precautions
Treatment begins with the smallest effective doses, with the reaction to the first administration watched closely, and the course is kept as short as possible: with prolonged use diazepam leads to physical and psychological dependence and to tolerance. Once dependence has formed, withdrawal causes an abstinence syndrome — headache and muscle pain, anxiety, restlessness, confusion and irritability, and in severe cases loss of consciousness, depersonalisation, sharpened hearing, hallucinations and seizures. A rebound phenomenon is also possible, with mood swings, anxiety and difficulty falling asleep; it is likelier after abrupt withdrawal, so the medicine is tapered off. The combination with opioids is singled out: it may lead to sedation, respiratory depression, coma and death, so prescribing them together is admissible only where there is no alternative, at the smallest dose and for the shortest time, having warned the patient and whoever cares for them. Anterograde amnesia is possible too — the loss from memory of events following administration.
Caution is needed in the elderly and the debilitated, in hepatic and renal failure, organic brain damage, ataxia, chronic respiratory failure even of moderate degree, and in prostatic enlargement with urinary retention: doses are reduced and the response is monitored. Newborns are not given the medicine, particularly if there are signs of prematurity; in infants under six months it is admissible only in exceptional, life-threatening cases. In children and the elderly paradoxical reactions cannot be ruled out — agitation, aggression, delusions, nightmares, hallucinations, psychosis — and if they appear the medicine is withdrawn. Diazepam is not an antipsychotic and cannot be the sole treatment for psychosis. In treated glaucoma benzodiazepines are used with great care, and in untreated glaucoma they are not recommended at all. Drug or alcohol dependence and personality disorders call for particular caution, and in acute poisoning with alcohol, hypnotics, painkillers, neuroleptics or antidepressants the medicine is not recommended. Alcohol after administration can cause pathological intoxication with agitation, aggression and memory gaps, so even small amounts are admissible no sooner than 36 hours after the last dose.
Interactions with other medicines
The first and most important group is everything that depresses the central nervous system: opioid painkillers, antipsychotics, antidepressants, anxiolytics, sedatives, hypnotics, anticonvulsants and anaesthetics, along with antihistamines that have a sedative effect. Combined use intensifies sedation, and disturbances of the respiratory centre and the cardiovascular system cannot then be ruled out. If diazepam nevertheless has to be given with an opioid painkiller, it is given last, and the dose and duration of the combined treatment are limited. Alcohol strengthens the effect of diazepam and can cause acute breathing disorders, so combining the two is not recommended.
The second group involves the liver. Cimetidine, omeprazole, fluoxetine, fluvoxamine, disulfiram, isoniazid and oral contraceptives slow the hepatic transformation of benzodiazepines and raise their serum concentration — that is, they strengthen and prolong the effect of an ordinary dose. Theophylline, by contrast, speeds up the metabolism of diazepam. Diazepam itself inhibits the action of levodopa and enhances the action of phenytoin and of skeletal muscle relaxants.
Pregnancy and breastfeeding
No safety studies of diazepam in pregnant women have been carried out. The medicine should not be used in pregnancy, especially in the first and third trimesters, unless in the doctor's judgement the benefit to the mother outweighs the potential threat to the foetus. The caveat about eclampsia matters here: it is among the indications precisely because that condition in itself threatens the lives of mother and child, and the decision is made by the doctor in the particular situation, not in advance.
The risk of administration during labour is described separately: a single large dose or repeated small ones caused hypothermia, muscular hypotonia, breathing disorders, floppy infant syndrome and disturbances of cardiac function in the newborn. Diazepam does pass into breast milk, so it should not be used while breastfeeding. To this the excipients add their own weight: propylene glycol crosses to the foetus and into milk, while ethanol and benzyl alcohol require separate consideration.
Adverse reactions
Adverse reactions after use of the medicine are usually mild and occur rarely. The expected part of them is a continuation of the main effect: sedation, drowsiness and incoordination of movement. Rarely recorded are headache and dizziness, disorientation, anterograde amnesia, speech disturbance and tremor, changes in the blood count, allergic skin reactions, visual disturbance, a fall in blood pressure, bradycardia, chest pain, breathing disorders, laryngeal spasm and apnoea. Less often described are dry mouth and increased appetite, jaundice, urinary retention, changes in libido, menstrual disturbance and fatigue; muscle weakness is listed separately.
Mental reactions stand apart. Paradoxical reactions are possible — restlessness, agitation, hallucinations, changes in behaviour, aggression, nightmares, psychosis — and they occur especially often in children and in the elderly; a previously hidden depression may surface during treatment. In elderly and debilitated patients the reactions run more severely. Physical dependence can develop even after therapeutic doses, and stopping administration can bring on an abstinence syndrome and a rebound phenomenon; psychological dependence and cases of abuse have been described.
Overdose
The manifestations of overdose are drowsiness and confusion. Mild cases, in which the person responds to a voice and breathing is unimpaired, need only symptomatic treatment. Severe ones run with ataxia, low blood pressure, muscle weakness and respiratory depression, rarely with coma; in those cases circulation and breathing are monitored and supported.
Benzodiazepines, unlike most medicines, have a specific antidote — flumazenil. It is given intravenously, starting with 0.2 mg over 15 seconds; if the desired level of consciousness is not reached within a minute, a second dose of 0.1 mg is injected and, if needed, repeated every minute up to a total of 1.0 mg, while intensive care units use larger doses. A diagnostic hint is hidden here as well: if flumazenil does not work, benzodiazepine poisoning is unlikely and the cause is sought elsewhere. Dialysis is ineffective in diazepam overdose.
How to get a RELSED prescription online
RELSED is dispensed on prescription, and at e-zdrowie.com it can be arranged remotely. You fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the microenemas against it. The request usually looks like this: the child has already had febrile convulsions, the neurologist advised keeping the medicine at home, and the parents need to replenish the supply.
So state who first prescribed the medicine and when, how many episodes of convulsions there have been, and also the child's age and exact weight — the weight decides whether the 5 mg or the 10 mg pack is needed. List the medicines being taken, above all anticonvulsants, opioid painkillers, antidepressants and hypnotics, and mention liver and kidney disease, breathing disorders, sleep apnoea and glaucoma. A first-ever convulsive seizure, a seizure lasting more than five minutes and any convulsions in a child under six months are grounds for urgent care in person, not for a remote prescription.
