Pregabalin Accord: composition and pharmaceutical form
Pregabalin Accord comes as hard capsules containing 25 mg, 75 mg, 150 mg or 300 mg of pregabalin.
That range of strengths is explained by the treatment scheme: the medicine is started at a small dose, raised in steps and withdrawn in steps just the same. The 25 mg capsules are needed above all in patients with impaired kidney function, where the daily dose may be very small. The medicine can be taken with food or independently of it.
How Pregabalin Accord works
Pregabalin binds to an auxiliary subunit — the α2-δ protein — of the voltage-dependent calcium channel in the central nervous system.
That is precisely what explains the wide range of indications, at first glance unrelated to one another: neuropathic pain, epileptic seizures and generalised anxiety. In all three cases the issue is excessive excitability of neurons, and that is what the medicine acts on.
Indications
Pregabalin is used in adults for neuropathic pain of peripheral and central origin, and also in generalised anxiety disorder.
The third indication is epilepsy, but with a caveat: the medicine is prescribed as part of combination treatment for partial seizures in adults, with or without secondary generalisation. The data are insufficient to withdraw other antiepileptics and move the patient to pregabalin monotherapy once seizure control has been achieved.
Method of use and dosage
The daily dose is 150 to 600 mg and is divided into 2–3 intakes. The start is always 150 mg a day, and the pace of increase depends on the indication and on tolerance.
| Indication or situation | Scheme |
|---|---|
| Neuropathic pain | 150 mg a day; after 3–7 days up to 300 mg; after another 7 days a maximum of 600 mg |
| Epilepsy | 150 mg a day; after a week up to 300 mg; a week later a maximum of 600 mg |
| Generalised anxiety disorder | 150 mg a day; then in weekly steps — 300 mg, 450 mg and a maximum of 600 mg |
| Creatinine clearance of 30–60 ml/min | a starting dose of 75 mg, a maximum of 300 mg a day in 2–3 intakes |
| Creatinine clearance of 15–30 ml/min | a starting dose of 25–50 mg, a maximum of 150 mg a day |
| Creatinine clearance below 15 ml/min | a starting dose of 25 mg, a maximum of 75 mg a day as a single intake |
Pregabalin is eliminated by the kidneys unchanged, and its clearance is directly proportional to creatinine clearance, so in renal impairment the dose is chosen individually. Haemodialysis removes half of the medicine from the plasma in 4 hours, so after each session an additional dose is given — from 25 to 100 mg as a single intake. In impaired liver function no adjustment is needed. Withdrawing the medicine, whatever the indication, should be gradual, over no less than a week.
Contraindications
The list consists of a single point.
- hypersensitivity to pregabalin or to any excipient of the medicine.
Special warnings and precautions
The medicine's most frequent effects — dizziness and drowsiness — have direct practical consequences: in elderly people they raise the risk of falls and injuries. After the medicine reached the market, loss of consciousness, confusion and psychiatric disturbances were also reported. The patient is therefore advised to be careful until it becomes clear how exactly the medicine affects them.
Vision, kidneys and metabolism
- blurred vision occurred in controlled studies more often than on placebo and usually passed as treatment continued;
- on ophthalmological examination, reduced visual acuity and changes in the visual fields were also more frequent on pregabalin;
- after the medicine reached the market, visual disturbances up to loss of vision have been described, often transient; stopping the medicine may make them disappear or lessen;
- cases of renal failure have been reported that sometimes resolved after the medicine was withdrawn;
- if swelling of the face, lips or upper airways appears the medicine is withdrawn at once: hypersensitivity reactions, including angioedema, have been described;
- patients with diabetes who gain weight during treatment may need the doses of their glucose-lowering medicines adjusted.
Withdrawal symptoms
In some patients, after stopping both short and long treatment, insomnia, headache, nausea, anxiety, diarrhoea, a flu-like state, nervousness, depression, pain, convulsions, increased sweating and dizziness occurred. These manifestations point to physical dependence, and the patient is warned of that possibility before treatment begins. That is precisely why the medicine is withdrawn gradually, over at least a week, rather than all at once.
Drug interactions
Pregabalin is excreted in the urine predominantly unchanged — less than 2% of the dose is eliminated as metabolites — does not inhibit the metabolism of other medicines in vitro and does not bind to plasma proteins. Pharmacokinetic interactions are therefore unlikely, which practice has confirmed: no significant interactions have been noted with phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Oral glucose-lowering agents, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant influence on the clearance of pregabalin, and concomitant use with oral contraceptives based on norethisterone and ethinylestradiol did not change the pharmacokinetics of either medicine.
What matters in practice are interactions of another kind — pharmacodynamic ones. Pregabalin can enhance the action of ethanol and lorazepam and, with oxycodone, probably acts additively on impairment of cognitive function and gross motor skills. In controlled studies, repeated use of pregabalin with oxycodone, lorazepam or ethanol had no clinically significant influence on breathing; however, after the medicine reached the market, cases of respiratory failure and coma were reported in patients taking pregabalin together with other agents depressing the central nervous system.
Pregnancy and breastfeeding
Since the risk to humans is unknown, women of childbearing age must use a reliable method of contraception. There are no sufficient data on the use of pregabalin in pregnant women, and animal studies showed a toxic effect on reproduction. The medicine should not be used in pregnancy unless the expected benefit to the mother substantially outweighs the risk to the foetus.
Pregabalin passes into breast milk, and its influence on the newborn's and the child's body is unknown. The decision whether to stop breastfeeding or treatment is taken by weighing the benefit of breastfeeding for the child against the benefit of therapy for the mother. There are no clinical study data on the influence on female fertility; in healthy men, taking 600 mg a day for 3 months had no influence on sperm motility, while in rats studies revealed an unfavourable influence on reproduction and development, the clinical significance of which is unknown.
Adverse effects
The clinical study programme covered more than 8900 patients. The most frequent adverse reactions are dizziness and drowsiness; they were usually mild or moderate, but it was precisely these that most often led to treatment being stopped. The proportion of withdrawals from the medicine because of adverse reactions was 12% against 5% on placebo.
- very common: dizziness, drowsiness, headache;
- common in the nervous system: ataxia, coordination disorders, tremor, speech disturbances, forgetfulness and memory impairment, difficulty concentrating, paraesthesia, reduced sensitivity, sedation, balance disturbances, lethargy;
- common in the psychic sphere: euphoria, confusion, irritability, disorientation, insomnia, reduced libido;
- common, other: increased appetite, blurred and double vision, nasopharyngitis;
- uncommon: fainting, stupor, myoclonic convulsions, loss of consciousness, dyskinesia, nystagmus, cognitive impairment, psychomotor hyperactivity, diminished reflexes, a burning sensation, loss of taste;
- uncommon in the psychic sphere: hallucinations, panic attacks, motor restlessness, agitation, depression, aggression, mood swings, depersonalisation, difficulty finding words, anorgasmia, apathy;
- uncommon in the eyes and metabolism: loss of visual fields, reduced visual acuity, eye pain, dryness and irritation of the eyes, watering, a sensation of flashes, anorexia, hypoglycaemia, neutropenia;
- rare: seizures, impaired sense of smell, hypokinesia, dysgraphia, disinhibition, loss of vision, keratitis, pupil dilation, squint, angioedema and allergic reactions.
The practical conclusion: dizziness and drowsiness most often appear at the start of treatment and when the dose is raised. Until it is clear how the medicine affects you in particular, it is better not to get behind the wheel.
Overdose
After the medicine reached the market, drowsiness, confusion, agitation and restlessness were most often observed in pregabalin overdose. Cases of coma were reported rarely.
Treatment consists of general supportive therapy and, if necessary, haemodialysis is used — pregabalin is efficiently removed from the plasma, and about half of the medicine is cleared in a 4-hour session. No specific antidote is required.
How to get a prescription for Pregabalin Accord online
Pregabalin Accord is a prescription-only medicine: the doctor chooses the starting dose and the pace of increase by indication, always takes kidney function into account and assesses compatibility with other medicines that depress the nervous system.
During the online consultation the doctor will clarify the nature of the pain or the anxiety, go through the medicines you take and determine the scheme. If the medicine is suitable, they will issue an electronic prescription and explain how to finish the course properly so as not to run into withdrawal symptoms.
