CHAPTER ONE

INTRODUCTION

1.1 BACKGROUND TO THE STUDY

Musculoskeletal pain is a common complaint presented to healthcare practitioners, significantly

impacting an individual's quality of life. Untreated or under-treated pain can lead to negative

consequences, making effective pain management crucial. Orphenadrine paracetamol is a

combination medication used to manage acute pain associated with muscle spasms and soft

tissue injuries. Orphenadrine acts as a muscle relaxant, while paracetamol provides analgesic and

antipyretic effects. The combination may offer increased antinociceptive activity and duration of

action. Studies have shown that orphenadrine paracetamol is effective in alleviating acute

musculoskeletal pain, muscle strains, sprains, tension headaches, and back pain. Generally well-

tolerated, with common side effects including drowsiness, dizziness, dry mouth, nausea, and

constipation. Contraindicated in individuals with liver or kidney disease, glaucoma, enlarged

prostate, or allergies to orphenadrine or paracetamol. Despite its widespread use, there is a need

for comprehensive evaluation of orphenadrine paracetamol's efficacy and safety in pain

management. This study aims to assess the clinical effectiveness and safety of this combination

medication in real-world settings.

1.2 STATEMENT OF THE PROBLEM

Reviewing the efficacy of orphenadrine and paracetamol can be challenging due to several

factors involving few high-quality studies, such as randomized controlled trials, or existing

studies may have methodological limitations or biases, differences in study design, population,

and outcome measures can make it difficult to compare results across studies as well as

1
variability in dosing regimens and treatment duration can also impact efficacy assessments. To

address the challenges associated with reviewing orphenadrine and paracetamol efficacy,

systematic reviews and meta-analyses to synthesize available evidence need to be conducted and

provision of a comprehensive overview of efficacy, rigorous methods should be used to

minimize bias and ensure reproducibility.

1.2 AIM OF THE STUDY

The aim of this medication review is to evaluate the efficacy and safety of orphenadrine and

paracetamol in pain management, providing a comprehensive overview of its benefits and risks.

1.4 RESEARCH QUESTIONS/HYPOTHESES

Research Questions

1. Efficacy:

- What is the efficacy of orphenadrine paracetamol in managing pain associated with

musculoskeletal conditions?

- Does orphenadrine paracetamol provide significant pain relief compared to placebo or other
pain management medications?

2. Safety:

- What are the common adverse effects associated with orphenadrine paracetamol?

- What is the risk of serious adverse events, such as liver damage or allergic reactions, with
orphenadrine paracetamol use?

3. Comparative Effectiveness:

- How does the efficacy and safety of orphenadrine paracetamol compare to other pain
management medications, such as NSAIDs or opioids?

- Is orphenadrine paracetamol a suitable alternative for patients who cannot tolerate or do not
respond to other pain medications?

2
Hypotheses

1. Orphenadrine paracetamol is effective in managing pain associated with musculoskeletal

conditions, with a favorable safety profile.

2. Orphenadrine paracetamol provides significant pain relief compared to placebo.

3. The efficacy and safety of orphenadrine paracetamol are comparable to other pain
management medications.

1.5 SIGNIFICANCE OF THE STUDY

This study is significant for several reasons:

1. Improved Pain Management:

- The study will provide valuable insights into the efficacy and safety of orphenadrine

paracetamol, enabling healthcare professionals to make informed decisions about its use in pain

management.

- Effective pain management can improve patients' quality of life, reduce healthcare utilization,

and minimize the risk of chronic pain.

2. Informed Decision-Making:

- The study's findings will inform clinical practice and guide treatment decisions, ensuring that

patients receive the most effective and safest treatment options.

- Healthcare professionals can use the study's results to weigh the benefits and risks of

orphenadrine paracetamol and make informed decisions about its use.

3. Patient Safety:

3
- The study will identify potential safety concerns associated with orphenadrine paracetamol,

enabling healthcare professionals to take steps to minimize risks and ensure patient safety.

- By understanding the safety profile of orphenadrine paracetamol, healthcare professionals can

better monitor patients and adjust treatment plans as needed.

1.6 SCOPE OF THE STUDY

The scope of this study is to conduct a comprehensive medication review of orphenadrine

paracetamol, focusing on its efficacy and safety in managing pain associated with

musculoskeletal conditions.

Inclusion Criteria:

- Studies evaluating the efficacy and safety of orphenadrine paracetamol in pain management.

- Studies involving patients with musculoskeletal conditions, such as muscle spasms, strains, and

sprains.

- Studies published in English language.

Exclusion Criteria:

- Studies evaluating orphenadrine or paracetamol as monotherapy.

- Studies involving patients with chronic pain conditions, such as arthritis or fibromyalgia.

- Studies with inadequate data or methodological flaws.

4
 CHAPTER TWO

LITERATURE REVIEW

2.1 LITERATURE REVIEW

The management of musculoskeletal pain is complex therefore plethora of treatment options are

available include non-pharmacological treatments , complementary therapies, and

pharmacological interventions. In order to provide optimal care to patients with musculoskeletal

pain and ensure the efficient use of healthcare resources, a comprehensive overview of the

available evidence for the most effective treatment options for musculoskeletal pain

presentations is essential. Musculoskeletal pain is a common complaint presented to healthcare

practitioners, significantly impacting an individual's quality of life. Untreated or under-treated

pain can lead to negative consequences, making effective pain management crucial.

Orphenadrine, a muscle relaxant and paracetamol anagelsic/antipyretic is a combination

medication used to manage acute pain associated with muscle spasms and soft tissue injuries.

Orphenadrine is a muscle relaxant that works by changing how your body senses muscle pain,

while paracetamol (also known as acetaminophen) is a pain reliever that helps reduce fever and

alleviate pain.

2.1.1 Mechanism of Action

Orphenadrine acts as a muscle relaxant, while paracetamol provides analgesic and antipyretic

effects. The combination may offer increased antinociceptive activity and duration of action.

2.1.2 Dosage

5
The usual dose for adults is 2 tablets 3 times daily, but it's essential to follow your doctor's

instructions. Do not take more than the recommended dose, and space each dose at least 4 hours

apart.

2.1.3 Side effects

Common side effects include:

- Gastrointestinal: Nausea, vomiting, dry mouth, constipation, and stomach upset

- Neurological: Drowsiness, dizziness, headache, and blurred vision

- Other: Fatigue, weakness, and nasal congestion

Serious side effects:

Rare but serious side effects may include⁵:

- Allergic reactions: Swelling of the face, lips, tongue, or throat, difficulty breathing, and itchy

skin rashes

- Liver problems: Dark urine, feeling tired, loss of appetite, and yellowing of the skin or eyes

- Heart problems: Fast heartbeat, palpitations

2.1.4 Precautions

- Avoid taking alcohol with orphenadrine and paracetamol, as it may increase drowsiness

- Inform your healthcare professional about any history of liver conditions, glaucoma, urinary

conditions, or enlarged prostate

6
- Do not exceed the recommended dose, and do not take other paracetamol-containing products

while on this medication

2.1.5 Storage

Store the medication in a cool, dry place, away from direct sunlight, and keep it out of reach of

children.

2.1.6 CHALLENGES

The use of orphenadrine and paracetamol can be associated with several challenges, including:

1. Side Effects: Common side effects include drowsiness, dizziness, dry mouth, nausea, and

constipation. These side effects can impact daily activities and quality of life.

2. Interactions: Orphenadrine can interact with other medications, such as sedatives,

anticholinergic drugs, and MAOIs, which may increase the risk of adverse effects.

3. Contraindications: Certain individuals, such as those with glaucoma, urinary retention, or

myasthenia gravis, may be contraindicated for orphenadrine use.

4. Liver Toxicity: Paracetamol can cause liver damage when taken in excessive amounts or

combined with other hepatotoxic substances.

5. Dependence and Withdrawal: Long-term use of orphenadrine can lead to dependence and

withdrawal symptoms when discontinued.

6. Dose Management: Finding the optimal dose can be challenging, as it may require balancing

efficacy with side effects.

7
7. Monitoring: Regular monitoring is necessary to assess efficacy, side effects, and potential

interactions.

8. Patient Education: Patients need to be educated about proper use, potential side effects, and

interactions to ensure safe and effective treatment.

Additional Considerations

- Age-Related Considerations: Older adults may be more susceptible to side effects and

interactions due to age-related changes in metabolism and organ function.

- Pregnancy and Lactation: The use of orphenadrine and paracetamol during pregnancy and

lactation should be carefully evaluated, considering potential risks and benefits.

2.1.7 MITIGATING THE CHALLENGES

To address the challenges associated with orphenadrine and paracetamol,

1. Dose Optimization

- Start with the lowest effective dose and titrate as needed to minimize side effects.

- Monitor patient response and adjust the dose accordingly.

2. Patient Education

- Educate patients about potential side effects, interactions, and proper use.

- Emphasize the importance of adhering to the prescribed dosage and reporting any concerns.

3. Monitoring

8
- Regularly monitor patients for efficacy, side effects, and potential interactions.

- Adjust the treatment plan as needed to ensure optimal outcomes.

4. Medication Management

- Review the patient's medication list to identify potential interactions.

- Consider alternative medications or adjust dosages to minimize interactions.

5. Contraindication Screening

- Carefully evaluate patients for contraindications, such as glaucoma or urinary retention, before

prescribing orphenadrine.

6. Liver Function Monitoring

- Monitor liver function in patients taking paracetamol, especially those with pre-existing liver

conditions or taking other hepatotoxic medications.

7. Dependence and Withdrawal Prevention

- Use orphenadrine for the shortest duration necessary to minimize the risk of dependence and

withdrawal.

- Gradually taper the dose when discontinuing treatment to prevent withdrawal symptoms.

8. Alternative Treatment Options

- Consider alternative treatments, such as physical therapy or other medications, for patients who

experience significant side effects or interactions.

9
2.2 MEDICATION REVIEW

A medication review is a thorough evaluation of a patient's medication regimen to ensure that it

is safe, effective, and appropriate for their specific needs. It involves a systematic assessment of

the medications being taken, including:

- Medication history: Reviewing the patient's current and past medications, including dosages

and duration of use.

- Medication appropriateness: Evaluating whether the medications are necessary, effective, and

safe for the patient.

- Medication interactions: Checking for potential interactions between medications, including

drug-drug, drug-disease, and drug-food interactions.

- Side effects and adverse reactions: Monitoring for potential side effects and adverse reactions,

and adjusting the medication regimen as needed.

2.2.1 EFFICACY

Efficacy refers to the ability of a medication to produce the desired therapeutic effect in a

controlled clinical setting. In other words, efficacy measures how well a medication works in

ideal circumstances, such as in a clinical trial.

- Therapeutic effect: The desired outcome of treatment, such as reducing symptoms, improving
quality of life, or curing a disease.

- Clinical trials: Studies that evaluate the efficacy and safety of a medication in a controlled
setting.

- Outcome measures: The specific measures used to assess the efficacy of a medication, such as
symptom reduction, quality of life, or survival rates.

10
2.2.2 SAFETY IN MEDICATION REVIEW

Safety in medication review refers to the evaluation of the potential risks and adverse effects

associated with a medication, with the goal of minimizing harm and ensuring safe use.

Key Aspects:

1. Adverse Event Monitoring: Identifying and monitoring adverse events, such as side effects,

allergic reactions, and medication interactions.

2. Risk Assessment: Evaluating the potential risks associated with a medication, including the

risk of adverse events, medication interactions, and contraindications.

3. Medication Interaction Identification: Identifying potential interactions between medications,

including drug-drug interactions, drug-disease interactions, and drug-food interactions.

4. Contraindication Identification: Identifying contraindications, such as allergies, pregnancy, or

certain medical conditions, that may affect the safe use of a medication.

5. Dose Adjustment: Adjusting the dose of a medication to minimize the risk of adverse events

and ensure safe use.

Goals:

1. Minimize Harm: Minimize the risk of adverse events and harm associated with medication

use.

2. Optimize Therapy: Optimize medication therapy to ensure safe and effective use.

3. Improve Patient Outcomes: Improve patient outcomes by reducing the risk of adverse events

and medication-related problems.

11
Importance:

Safety in medication review is crucial to ensure the safe and effective use of medications,

particularly for patients with complex medication regimens or those at high risk of adverse

events.

Benefits:

1. Reduced Adverse Events: Reduced risk of adverse events and medication-related problems.

2. Improved Patient Safety: Improved patient safety and reduced risk of harm.

3. Optimized Medication Therapy: Optimized medication therapy, leading to better patient

outcomes.

2.3 PROCEDURE TO REVIEW THE EFFICACY AND SAFETY OF

ORPHENADRINE AND PARACETAMOL

Step 1: Define the Review Question

- Clearly define the review question, including the population, intervention, comparison, and

outcomes (PICO).

- Example: "What is the efficacy and safety of orphenadrine and paracetamol compared to

placebo or other pain management medications in patients with musculoskeletal pain?"

Step 2: Develop a Protocol

- Develop a protocol that outlines the review's objectives, methodology, and inclusion/exclusion

criteria.

12
- Register the protocol with a review registry, such as PROSPERO.

Step 3: Literature Search

- Conduct a comprehensive literature search of major databases, including:

- PubMed

- Scopus

- Cochrane Library

- Web of Science

- Use relevant keywords, such as "orphenadrine," "paracetamol," "pain management," and

"efficacy and safety."

Step 4: Study Selection

- Identify relevant studies that evaluate the efficacy and safety of orphenadrine and paracetamol.

- Apply inclusion and exclusion criteria to select studies that meet the review's objectives.

Step 5: Data Extraction

- Extract relevant data from selected studies, including:

- Study design and methodology

- Patient population and demographics

- Efficacy outcomes (e.g., pain relief, functional improvement)

- Safety outcomes (e.g., adverse events, side effects)

13
Step 6: Quality Assessment

- Assess the quality of selected studies using standardized tools, such as:

- Cochrane Risk of Bias Tool

- Newcastle-Ottawa Scale

- Evaluate the risk of bias, study design, and reporting quality.

Step 7: Data Analysis

- Analyze extracted data to evaluate the efficacy and safety of orphenadrine and paracetamol.

- Use statistical methods, such as meta-analysis, to combine data from multiple studies.

Step 8: Results Interpretation

- Interpret the results of the review, focusing on the efficacy and safety of orphenadrine and

paracetamol.

- Consider the quality of evidence, study limitations, and potential biases.

Step 9: Conclusion and Recommendations

- Draw conclusions about the efficacy and safety of orphenadrine and paracetamol.

- Provide recommendations for clinical practice, based on the review's findings.

Step 10: Reporting

- Report the review's findings in a clear and transparent manner, following established

guidelines, such as PRISMA.

14
- Ensure that the report includes:

- A detailed description of the review's methodology

- A summary of the findings, including efficacy and safety outcomes

- Implications for clinical practice and future research

2.3.1 CHALLENGES FACED DURING REVIEW

Reviewing the efficacy of orphenadrine and paracetamol can be challenging due to several

factors:

1. Limited High-Quality Evidence

- Few high-quality studies, such as randomized controlled trials, may be available to assess

efficacy.

- Existing studies may have methodological limitations or biases.

2. Variability in Study Design

- Differences in study design, population, and outcome measures can make it difficult to compare

results across studies.

- Variability in dosing regimens and treatment duration can also impact efficacy assessments.

3. Subjective Outcome Measures

- Pain is a subjective outcome, and measurement tools may not always accurately capture the

patient's experience.

15
- Patient-reported outcomes may be influenced by various factors, such as expectations and

emotional state.

4. Short-Term Focus

- Many studies focus on short-term efficacy, and long-term effects may not be well understood.

- Chronic pain management may require a different approach than acute pain management.

5. Heterogeneous Patient Populations

- Patients with different underlying conditions, such as musculoskeletal pain or tension

headaches, may respond differently to treatment.

- Variability in patient characteristics, such as age and comorbidities, can impact efficacy

assessments.

6. Potential for Bias

- Studies may be influenced by biases, such as publication bias or selective reporting.

- Industry sponsorship or conflicts of interest may also impact study results.

7. Lack of Standardized Outcome Measures

- Different studies may use different outcome measures, making it challenging to compare

results.

- Standardized outcome measures can help facilitate more accurate comparisons.

8. Limited Generalizability

16
- Study results may not be generalizable to real-world settings or diverse patient populations.

- Differences in clinical practice, patient characteristics, and treatment settings can impact

efficacy.

2.3.2 SOLUTION

To address the challenges associated with reviewing orphenadrine and paracetamol efficacy, the

following should be considered:

1. Systematic Review and Meta-Analysis

- Conduct systematic reviews and meta-analyses to synthesize available evidence and provide a

comprehensive overview of efficacy.

- Use rigorous methods to minimize bias and ensure reproducibility.

2. Standardized Outcome Measures

- Use standardized outcome measures, such as validated pain scales, to facilitate comparisons

across studies.

- Ensure that outcome measures are relevant to the patient population and treatment goals.

3. High-Quality Study Design

- Design studies with robust methodologies, such as randomized controlled trials, to minimize

bias and ensure internal validity.

- Use adequate sample sizes and ensure that studies are powered to detect significant differences.

4. Long-Term Follow-Up

17
- Include long-term follow-up in study designs to assess the durability of treatment effects.

- Evaluate the impact of treatment on quality of life, functional ability, and other relevant

outcomes.

5. Patient-Centered Outcomes

- Incorporate patient-centered outcomes, such as patient-reported outcomes and quality of life

measures, to capture the patient's experience.

- Use validated instruments to ensure that outcomes are measured accurately and reliably.

6. Subgroup Analysis

- Conduct subgroup analyses to identify potential differences in treatment response based on

patient characteristics, such as age or underlying condition.

- Use these analyses to inform treatment decisions and optimize patient care.

7. Transparency and Disclosure

- Ensure transparency in study design, methodology, and results.

- Disclose potential conflicts of interest and industry sponsorship to maintain credibility and

trustworthiness.

8. Collaboration and Knowledge Sharing

- Foster collaboration among researchers, clinicians, and patients to share knowledge and best

practices.

18
- Encourage open discussion and debate to refine understanding and improve treatment

approaches.

19
 CHAPTER THREE

METHODOLOGY

3.1 Study populations:

Patients suffering from painful musculoskeletal disorders includes ankle and knee sprains, non-

articular low-back pain, painful shoulder lesions (rotator cuff syndrome) and a variety of occupational

and sport injuries of the soft tissues in random order. In each case, subjective measures of pain, muscle

spasm, stiffness and other symptoms of the musculoskeletal pain was assessed through Muscle & Joint

Measure Scale (MJM).

Sample size

Patients included in the study were aged 18-59 years old, who presented with acute (less than 4 weeks) of

non-specific musculoskeletal pain.

3.3 Study design

Mixed method.

3.4 Inclusion Criteria of the study group

 Patient with a clinical history of painful musculoskeletal disorder from last 1 year

 Patient aged ≥18 and ≤70 years inclusive of either sex

 Patient with ability to understand and sign written informed consent form.

3.5 Exclusion Criteria of the study group

Patients that were excluded from the study:

(1) Those who were hypersensitive to either orphenadrine citrate or paracetamol

(2) Those who used any other oral preparations like NSAIDs, cyclobenzaprine, methocarbamol, or

opioids for the past 48 hours prior to initiation of treatment

20
(3) Those who were undergoing any other non-pharmacologic therapies for the pain, including

complementary and alternative medicine modalities (e.g., acupuncture, acupressure, therapeutic

massage, etc.)

(4) Those who were pregnant; or

(5) Those who had glaucoma, prostatic hypertrophy, bladder neck obstruction, or myasthenia gravis.

3.6 Instrument of Data Collection

3.6.1 Questionnaire

A self-administered structured questionnaire was used to interview the study group. The data obtained is

available as (Appendix A).

3.6.2 Interview

One on one interview was carried out with selected Nurses, Physicians, and inpatients to informed

knowledge about the study group.

3.7 Method of data collection

The method used to gather information from the respondents were through questionnaires, interviews, and

personal observation. Data were collected over a period of three weeks. The questionnaires were

distributed to the respondents and collected after completion. In-depth interviews were conducted in

person, recorded (with consent), and later transcribed for analysis.

3.8 Procedure for data collection

Study participants were prescribed with orphenadrine citrate 35 mg + paracetamol 450 mg (Norgesic®)

one to two tablets three times a day for a maximum of ten (10) days. They were followed up until the

resolution of their pain or until a maximum of ten (10) days were reached. Sixty (60) tablets were given for

free to study participants upon consultation. Participating physicians included primary care physicians,

general medical practitioners, family, physicians, community medicine and public health practitioners,

21
general internists, rehabilitation medicine specialists/physiatrists, and orthopedic surgeons. Patient

demographic and baseline characteristic data were collected on all patients that included age, sex, and

nature of work or profession. Pain intensity was measured by the visual analog scale (VAS), wherein, a 20-

mm reduction in pain intensity was considered statistically significant. Roland-Morris Disability

Questionnaire was used to evaluate the selfrated physical disability resulting from the pain of the patients.

Assessments were conducted both at the beginning (baseline) and upon completion of the study (day 11).

The primary endpoints of interest of the study were: (1) the decrease in VAS scores for pain from the

baseline until the total resolution of pain, possibly with no recurrence for a maximum of ten (10) days; (2)

the decrease in physical disability scores from baseline until completion of study; and (3) the time to total

resolution of pain after use of orphenadrine citrate 35 mg + paracetamol 450 mg, again with non-recurrence

of discomfort.

The secondary endpoints of the study were: (1) the time to total resolution of pain after use of orphenadrine

citrate 35 mg + paracetamol 450 mg, again with non-recurrence of pain; (2) the decrease in VAS score of

two (2) from baseline; (3) time to onset of pain relief after first dose,( 4) duration of pain free period after

first dose; (5) the decrease in physical disability scores from baseline until completion of study; and (6)

occurrence of adverse effects, including but not limited to, hypersensitivity reaction.

Daily dose of orphenadrine citrate 35 mg + paracetamol 450 mg was described and the number of drugs per

day was tabulated. Study participants who discontinued usage of orphenadrine citrate 35 mg + paracetamol

450 were reported and reasons for stopping was noted and collated.

No special protocol-mandated visits or procedures were associated with the study since this was an

observational, and uncontrolled study. Study participants were allowed to switch their treatment during the

study, but were encouraged to continue the given medication. Attending physicians were advised to

encourage patients to follow-up at least once (i.e. on day 11 as end of the treatment). Follow-up was done

22
as either via face-to-face or teleconsult. The VAS and physical disability scores were gathered after

initiation of treatment (shown in table 3).

Incidence rates with respective 95% confidence intervals (CI) were calculated, when applicable, for

selected safety outcomes. Continuous variables were expressed as mean ± SD or median (min and max) for

non- normally distributed data. Categorical variables were expressed as percentages. Significant differences

in VAS scores and number of tablets consumed between baseline and each succeeding day up to ten (10)

days was determined using Wilcoxon signed rank test. Likewise, differences in physical disability scores

between baseline and end of study period were determined using Wilcoxon signed rank test. A p-value

<0.05 was accepted to be statistically significant. Data were analyzed using Stata version 13 software.

3.9 Method of data analysis

Data obtained were analyzed using the following methods;

3.9.1 Flow chart sheet

A flow chart sheet was completed to assess the outcomes of the intervention. (Appendix B)

3.10 Ethical Considerations

This study adhered to ethical principles throughout its execution:

• Informed consent was obtained from all participants after explaining the purpose of the

study, their rights, and confidentiality assurances.

• Participants were assured of anonymity and voluntary participation, and they were free to

withdraw at any time without penalty.

• Data collected were stored securely and used only for academic purposes.

23
 CHAPTER FOUR

RESULT

4.1 Patients’ criteria at the time of entering the study:

There were 25 study participants, 56% of whom were females and 44% of whom were males with a mean age

of 38.3 SD ± 10.5 years. Forty two (40) % were white-collar workers, 36% were blue-collar workers, and 6%

were unemployed (Table 1).

Table (1): Shows respondents’ demography

Gender (n, %)

Male 11 (44)

Female 14 (56)

No answer (0)

Age in Years (mean, SD) 38.3, 10.5

Work/Profession

White-Collar (administration officer, accountant, BPO agent, businessman,

clerk/secretary, educator, engineer, encoder/IT, lawyer, medical staff) 10 (40)

Blue-Collar (construction worker, cook, driver, factory worker, farmer, gardener, 9 (36)
housekeeper, vendor, janitor,warehouse personnel)
Unemployed 6 (24)

No response (0)

The median onset of pain relief occurred an hour after the first dose of Norgesic® tablet, the fastest by

30 minutes and the slowest by the eight (8th) hour. The median length of time after the first dose and

24
before the next episode of pain was six (6) hours, with one hour as the shortest and 24 hours as the

longest period of relief from pain. Ninety (84)% were compliant to the medications. Non-compliance

was attributed to immediate pain relief and pain perceived as tolerable (Table 2).

Table (2): Shows Clinical outcomes of respondents

Onset of pain relief in hours after the first dose (median, minimum/ 1 (30 minutes, 8 hours)
maximum)
Duration of pain-free period before the next dose in hours after the first dose 6 (1 hour, 24 hours)
(median, minimum/maximum)
Compliance to medications (n, %)

Yes 21 (84)
No 3 (12)
No response 1 (4)

At baseline, the median VAS score was seven (7), with two (2) as the lowest and ten (10) as the

highest. Except for a unit increase in median VAS score, from four (4) at bedtime of day 1 to five (5)

on the morning of day 2, there was a decreasing trend observed on subsequent time points which

differed significantly from baseline (p<0.0001). It was only on day 7 when VAS scores dropped to zero

(0) until day 10. The median number of Norgesic® tablets consumed for pain relief likewise decreased

from three (3) tablets on day 1 to one (1) tablet on day 7 to none (0) on the succeeding days till end of

study period. The number of tablets consumed obviously coincided with the decrease in VAS scores to

zero (0) by day 7. The number of tablets consumed on day 2 and day 3 did not differ significantly from

baseline (p=0.1121 and p=0.2547, respectively) but reached statistical significance by day 4 until day

10 (p<0.0001) (Table 3).

Table (3): Shows VAS scores and number of tablets consumed from Day 1 to Day 10.
Time VAS p-value* p-value* Number of p-value*
scores tablets
consumed
Median Min. Max Median Min.
Max

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Day 1 3 1,9
Baseline 7 2,10
After 60 6 0,10 <0.0001
minutes
At bedtime 4 0,10 <0.0001
Day 2 3 0,9 0.1121
After 60 5 0, 10 <0.0001
minutes
At bedtime 4 0, 10 <0.0001
Day 3 3 0,9 0.2547
After 60 4 0, 9 <0.0001
minutes
At bedtime 3 0, 9 <0.0001
Day 4 2 0, 8 <0.0001 3 0,9 <0.0001
Day 5 1 0, 8 <0.0001 3 0, 6 <0.0001
Day 6 1 0, 8 <0.0001 3 0, 6 <0.0001
Day 7 0 0, 6 <0.0001 1 0, 6 <0.0001
Day 8 0 0, 6 <0.0001 0 0, 6 <0.0001
Day 9 0 0, 6 <0.0001 0 0, 6 <0.0001
Day 10 0 0, 6 <0.0001 0 0, 6 <0.0001
*Wilcoxon signed-rank test

The mean duration of pain before total resolution, which meant having a VAS score equal to zero (0)

with no recurrence of symptoms, was 5.1 SD ± 2.2 days. As many as 72% of the study participants had

a decrease of at least two (2) points from baseline in their VAS scores on day 1. This increased to 84%

by day 3, 96% by day 5, and 96% by day 6. From day 7 onwards, 100% of the participants exhibited a

decrease of more than two (2) points from baseline in their VAS scores (Table 4). The VAS score of

the lone participant with less than two (2) points decrease from baseline was six (6) with a baseline

value of seven (7). In most of the study participants, it was a 6-point decline each day from day 5 to day

10. The incremental increase in the proportion of those with complete resolution (VAS score=0) was

highest by day 7 with 14.9 percentage points difference from day 6 versus a 10.5 percentage points

difference from day 8, suggesting that most cases were completely resolved by day 7 (Table 4).

Table (4): Duration of symptoms before complete resolution and proportion of resolved cases

26
Duration of low back pain before complete resolution (VAS=0) with 5.1, 2.2
no recurrence in days (mean, SD)

Time in days Proportion of those whose VAS scores Proportion of those with
decreased by at least two (2) points from complete resolution (VAS=0), n
baseline, n (%) (%)

Day 1 18 (72) 1(4)

Day 2 20 (80) 2(8)

Day 3 21 (84) 4 (16)

Day 4 23 (92) 5 (20)

Day 5 24 (96) 9 (36)

Day 6 24 (96) 12 (48)

Day 7 25 (100) 15 (60)

Day 8 25 (100) 18 (72)

Day 9 25 (100) 19 (76)

Day 10 25 (100) 21 (84)

The median physical disability score on day 1 was nine (9), with a minimum value at zero (0) and a
maximum value at 25. On day 11, this decreased significantly to zero (0), with values ranging from
zero (0) to 16 (p<0.0001) (Table 5).

Table (5): Physical disability scores.

Physical Disability Scores Media Minimum p-value*
n ,
Maximum
Day 1 11 0, 25
<0.0001
Day 11 0 0, 16

Adverse events were reported in 22 study participants which consisted of the following: nausea
and vomiting (1), dry mouth (2), dizziness (6), somnolence (12), and blurring of vision (1). They

27
were generally mild, lasting for a minimum of one day to a maximum of six (6) days and
resolved spontaneously with rest (Table 6).

Table (6): Adverse events

Adverse Event Total Severity Duration in Action Outcome

days

Nausea and vomiting 1 Mild 3 No response No response

Dry mouth 2 Mild 2 water (2) resolved (2)

Dizziness 6 Mild (5) 2 (1), sleep (1) improved (2)

Moderate (1) 6 (4) no response (5) no response
3 (1) (4)
1 (1) none (2) improved (6)
Somnolence 12 Mild 3 (3) rest/sleep (5) no response
4 (2) no response (5) (6)
6 (5)
unspecified (1)

Blurring of vision 1 Mild 2 none Resolved

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 CHAPTER FIVE

CONCLUSION AND RECOMMENDATION

5.1 Conclusion:

Acute musculoskeletal pain is a common medical condition that afflicts millions of people

worldwide. It is not only considered a physical burden amongst patients, but it also impacts on

the social, economic, and psychological aspects of patients. Holistic management of acute

musculoskeletal pain entails both nonpharmacological interventions and medical therapy. The

single pill combination of orphenadrine 35 mg and paracetamol 450mg (Norgesic®) is effective

in alleviating pain, with complete resolution of pain being noted after seven days of treatment, as

well as in improving perceived disability scores. Self-limiting adverse events were reported with

Norgesic® use, but over-all safety of and tolerance to the combination pill were also

documented.

5.2 Recommendation:

Orphenadrine and paracetamol is a widely recognized combination medication for pain

relief, particularly in musculoskeletal conditions. This dual-action approach combines the

muscle relaxant effects of orphenadrine with the analgesic properties of paracetamol,

providing effective pain management. However, it's essential to follow prescribed dosages

and consult with a healthcare professional to minimize potential side effects

and interactions.

29
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