Baclofen is a muscle-relaxant drug. Baclofen is used to reduce and relieve the excessive tension in muscles (spasms) occurring in various illnesses such as cerebral palsy, multiple sclerosis, cerebrovascular accidents, spinal cord diseases and other nervous system disorders.
Palmitoylethanolamide (PMAE) is an endogenous fatty acid amide, belonging to the class of nuclear factor agonists. PMAE has been demonstrated to bind to a receptor in the cell-nucleus (a nuclear receptor) and exerts a great variety of biological functions related to chronic pain and inflammation.
Baclofen is commonly compounded as a topical 2-5% vaginal cream and our PMAE supplement is available as a 600mg chewable tablet.
Chemically, baclofen is a derivative of the neurotransmitter γ-aminobutyric acid (GABA). It is believed to work by activating (or agonizing) GABA receptors, specifically the GABAB receptors.2 Its beneficial effects in spasticity result from its actions in the brain and spinal cord.1
In patients suffering from vulvodynia, an exaggerated response to inflammation due to a decreased ability to downregulate the inflammatory activity is currently seen as a cornerstone in disease pathogenesis.3 Vulvodynia has been recognized as a cytokine-mediated pain syndrome, characterized by increases in proinflammatory cytokines i.e IL-8, and decreases in anti-inflammatory cytokines i.e. IL-10.4 Localized neuroinflammation may alter ion channel activity of peripheral axons, resulting in. sensitization and enhanced perception of pain in the local area.5
Within the context of neuroinflammation, it would be very likely that the synthesis of the autocoid bioactive lipids from the classes N-acylethanolamides (among which palmitoylethanolamide) is disturbed. Topical and systemic replenishment of PMAE may bring relief from pain by targeting tissue components of the vaginal epithelium, such as free nerve endings of nociceptors, immunocompetent cells, and epithelial cells.
Case Report 1
A 33-year-old woman with intractable chronic vulvar and anal pain had to abstain from sexual intercourse and could neither cycle nor sit for more than 5 min. The patient did not respond to standard treatments.
She was prescribed a combination of topical baclofen 5 % and palmitoylethanolamide 400 mg, three times daily. After 3 months, her symptoms decreased more than 50 % and sexual intercourse was possible again without pain.6
Case Report 1
In a retrospective evaluation of 38 patients with provoked vestibulodynia (PV), 2% amitriptyline and 2% baclofen cream was used. After 33 weeks of treatment, 53% of women reported much (>60%) improvement, 18%, reported moderate (30-60%) improvement , and 29% reported no or little (<30%) improvement. On self-administered questionnaires, patients reported a decrease in the extent to which the condition interfered with social activities (p=0.17), easier lubrication (p=0.22), and lower pain with intercourse (p=0.05). No patients experienced systemic side effects.7
Baclofen and PMAE have been used in women with vulvar pain syndromes.4,6,7
Apply Baclofen 2-5% to vulvar area three times daily & PMAE 600mg orally (chewed) twice daily.
Anesthetics. Anesthetic agents may potentiate the CNS effects of baclofen.
Antidepressants. The concomitant administration of baclofen and tricyclic antidepressants may potentiate the pharmacological effects of baclofen, resulting in pronounced muscular hypotonia. In addition, concomitant use of tricyclic antidepressants can cause sedation, drowsiness and potentiate the effects of baclofen resulting in pronounced muscular hypotonia.
Lithium. Concomitant use of oral baclofen and lithium resulted in aggravated hyperkinetic symptoms. Caution should be exercised when baclofen is used concomitantly with lithium.
MAO Inhibitors. The concurrent use of MAO inhibitors and baclofen may result in increased CNS-depressant effects; therefore, caution is advised and the dosage of one or both agents should be adjusted accordingly.
Antihypertensives. Since combined treatment with baclofen and antihypertensives is may increase the fall in blood pressure, the dosage of antihypertensive medication may need to be adjusted accordingly.
Levodopa/Dopa Decarboxylase (DDC) inhibitor (Carbidopa). In patients with Parkinson's disease receiving treatment with baclofen and levodopa (alone or in combination with a DDC inhibitor, carbidopa), there have been several reports of mental confusion, hallucinations, headache, nausea and agitation. Worsening of the symptoms of Parkinsonism has also been reported. Hence, caution should be exercised during concomitant administration of baclofen and levodopa/carbidopa.
Antidiabetic Agents. Isolated cases of increased blood glucose concentrations have been reported with baclofen; dosage adjustments of antidiabetic agents (oral and insulin) may therefore be necessary with combined baclofen treatment.
Neuromuscular Blocking Agents. Caution should be exercised when administering baclofen and magnesium sulfate (or other neuromuscular blocking agents), since a synergistic effect may theoretically occur.
Agents reducing renal function. Drugs or medicinal products that can significantly impact renal function (ex: memantine, NSAIDS) may reduce baclofen excretion leading to toxic effects.
Drugs Causing CNS depression. Increased sedation may occur when baclofen is taken concomitantly with other drugs causing CNS depression, including other muscle relaxants (such as tizanidine), synthetic opiates, hypnotics, anxiolytics or alcohol. The risk of respiratory depression is also increased. In addition, hypotension has been reported with concomitant use of morphine and intrathecal baclofen. Careful monitoring of respiratory and cardiovascular functions is essential, especially in patients with cardiopulmonary disease and respiratory muscle weakness.
Although Nyirjesy7 reported no systemic side effects with topical baclofen therapy, the most common effect when taken orally is transient drowsiness (10 to 63%). In one controlled study of 175 patients, transient drowsiness was observed in 63% of those receiving baclofen compared to 36% of those in the placebo group. Other common adverse reactions are dizziness (5 to 15%), weakness (5 to 15%) and fatigue (2 to 4%).
Neuropsychiatric: Confusion (1 to 11%), headache (4 to 8%), insomnia (2 to 7%); and, rarely, euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, coordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizure.
Cardiovascular: Hypotension (0 to 9%). Rare instances of dyspnea, palpitation, chest pain, syncope.
Gastrointestinal: Nausea (4 to 12%), constipation (2 to 6%); and rarely, dry mouth, anorexia, taste disorder, abdominal pain, vomiting, diarrhea, and positive test for occult blood in stool.
Genitourinary: Urinary frequency (2 to 6%); and rarely, enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, hematuria.
Other: Instances of rash, pruritus, ankle edema, excessive perspiration, weight gain, nasal congestion. Some of the CNS and genitourinary symptoms may be related to the underlying disease rather than to drug therapy. The following laboratory tests have been found to be abnormal in a few patients receiving baclofen: increased SGOT, elevated alkaline phosphatase, and elevation of blood sugar.
Although Nyirjesy7 reported no systemic side effects with topical baclofen therapy, patients should be cautioned regarding the operation of automobiles or other dangerous machinery, and activities made hazardous by decreased alertness due to the possibility of sedation. Patients should also be cautioned that the central nervous system effects of baclofen may be additive to those of alcohol and other CNS depressants.
Baclofen should be used with caution where spasticity is utilized to sustain upright posture and balance in locomotion or whenever spasticity is utilized to obtain increased function.
In patients with epilepsy, the clinical state and electroencephalogram should be monitored at regular intervals, since deterioration in seizure control and EEG have been reported occasionally in patients taking baclofen.
Baclofen should be used in caution in patients with underlying bladder sphincter hypertonia, since acute retention may occur.
Patients suffering from psychiatric conditions such as psychosis, schizophrenia, or confusional states should be treated cautiously with baclofen and kept under close surveillance, since exacerbation of these conditions may occur with baclofen treatment.
Baclofen is a pregnancy category C drug. There are no adequate and well-controlled studies that have been performed with pregnant women. Baclofen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Baclofen is excreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug since many drugs are excreted in human milk.
There is no data on baclofen or PMAE use in pediatric populations.
Caution should be exercised while administering baclofen in patients with renal impairment. Baclofen should be avoided in patients with kidney disease stage 3B (moderate), chronic kidney disease stage 4 (severe), chronic kidney disease stage 5 (failure).
No studies have been performed in patients with hepatic impairment receiving baclofen therapy. As baclofen does not undergo predominant hepatic metabolism, its pharmacokinetics is unlikely to be altered to a clinically significant level in patients with hepatic impairment. In rare instances, elevated SGOT, alkaline phosphatase and glucose in serum levels have been reported while using oral baclofen.
- Absorption: [Local] within 10 minutes
- Metabolism: [Systemic] 15% Liver by deamination
- Excretion: [Systemic] 85% is excreted unchanged in the urine and feces. Excretion is complete within 72hours after administration
PMAE is metabolized by the cellular enzymes fatty acid amide hydrolase (FAAH) and N-acylethanolamine acid amide hydrolase (NAAA), the latter of which has more specificity toward PMAE over other fatty acid amides
Overdosage of baclofen include vomiting, muscular hypotonia, drowsiness, accommodation disorders, coma, respiratory depression and seizures.
Store at room temperature.
- Brayfield, A, ed. (9 January 2017). "Baclofen: Martindale: The Complete Drug Reference". MedicinesComplete. London, UK: Pharmaceutical Press. Retrieved 15 August 2017.
- Facci, L.; Dal Toso, R.; Romanello, S.; Buriani, A.; Skaper, S. D.; Leon, A. (1995). "Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide". PNAS. 92 (8): 3376–3380.
- Eppsteiner E, Boardman L, Stockdale CK. Vulvodynia. Best Pract Res Clin Obstet Gynaecol. 2014;28(7):1000–1012
- Keppel Hesselink JM, Kopsky DJ, Sajben NL. Vulvodynia and proctodynia treated with topical baclofen 5% and palmitoylethanolamide. Arch Gynecol Obstet. 2014;290(2):389–393.
- Akopians AL, Rapkin AJ. Vulvodynia: the role of inflammation in the etiology of localized provoked pain of the vulvar vestibule (vestibulodynia). Semin Reprod Med. 2015;33(4):239–245.
- Keppel Hesselink, J.M., Kopsky, D.J. & Sajben, N.L. Arch Gynecol Obstet (2014) 290: 389.
- Nyirjesy, Paul MD1; Lev-Sagie, Ahinoam MD2; Mathew, Leny MS1; Culhane, Jennifer F. PhD. Topical Amitriptyline-Baclofen Cream for the Treatment of Provoked Vestibulodynia. J. Lower Urinary Tract Disease. 2009;13(4):230-236.
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