Voltfast Sep 2022.SIN Page 1 of 14
TRADE-NAME(S)
Voltfast
®
Anti-inflammatory and anti-rheumatic product, non-steroid, acetic acid derivative and related
substance.
DESCRIPTION AND COMPOSITION
Pharmaceutical form
Powder for oral solution.
Homogenous, white to light yellow powder.
Active substance
The active ingredient is diclofenac potassium. One Voltfast
®
sachet contains 50 mg of
diclofenac potassium.
Certain dosage strengths and dosage forms may not be available in all countries.
Excipients
Potassium hydrogen carbonate; mannitol; aspartame; saccharin sodium; glyceryl dibehenate;
mint flavor; anise flavor.
Pharmaceutical formulations may vary between countries.
INDICATIONS
As a short-term treatment (up to one week) for the relief of acute pain states in which there is an
inflammatory component.
Treatment of acute migraine attacks (with or without aura).
Symptomatic treatment of primary dysmenorrhoea.
DOSAGE REGIMEN AND ADMINISTRATION
Dosage regimen
As a general recommendation, the dose should be individually adjusted. Adverse effects may be
minimized by using the lowest effective dose for the shortest duration necessary to control
symptoms (see section WARNINGS AND PRECAUTIONS).
General target population
Adults
The recommended initial daily dose is 100 to 150 mg. In milder cases, 50 to 100 mg daily are
usually sufficient. The daily dose should generally be divided in up to 3 separate doses.
In primary dysmenorrhoea, the daily dose should be individually adjusted and is generally 50
to 150 mg. A dose of 50 to 100 mg should be given initially and, if necessary increased over the
course of several menstrual cycles up to a total maximum of 200 mg/day. Treatment should
Voltfast Sep 2022.SIN Page 2 of 14
be started on appearance of the first symptoms and, depending on the symptomatology, continued
for a few days.
In migraine, an initial dose of 50 mg should be taken at the first signs of an impending attack.
In cases where pain relief within 2 hours after the first dose is not sufficient, a further dose of
50 mg may be taken. If needed, further doses of 50 mg may be taken at intervals of 4 to 6
hours, not exceeding a total dose of 200 mg per day.
Special populations
Renal impairment
Voltfast is contraindicated in patients with renal failure (GFR <15 mL/min/1.73 m
2
) (see section
CONTRAINDICATIONS).
No specific studies have been carried out in patients with renal impairment, therefore, no
specific dose adjustment recommendations can be made. Caution is advised when administering
Voltfast to patients with renal impairment (see section WARNINGS AND PRECAUTIONS).
Hepatic impairment
Voltfast is contraindicated in patients with hepatic failure (see section CONTRAINDICATIONS).
No specific studies have been carried out in patients with hepatic impairment, therefore, no
specific dose adjustment recommendations can be made. Caution is advised when administering
Voltfast to patients with mild to moderate hepatic impairment (see section WARNINGS AND
PRECAUTIONS).
Pediatric patients (below 18 years)
Voltfast 50 mg powder for oral solution is not recommended for use in children and adolescents
below 14 years of age; other forms of diclofenac such as oral drops or suppositories could
be used in these patients.
For adolescents aged 14 years and over, a daily dose of 50 to 100 mg is usually sufficient.
The total daily dose should generally be given as 1 to 2 divided doses.
The use of Voltfast 50 mg powder for oral solution in migraine attacks has not been established
in children and adolescents.
Geriatric patients (65 years of age or above)
No adjustment of the starting dose is generally required for elderly patients. However, caution
is indicated on basic medical grounds, especially for frail elderly patients or those with a low
body weight. Although the pharmacokinetics of Voltfast are not impaired to any clinically
relevant extent in elderly patients, Voltfast should be used with particular caution in such
patients who generally are more prone to adverse reactions. (see section WARNINGS AND
PRECAUTIONS).
Established cardiovascular disease or significant cardiovascular risk factors
The use of high dose diclofenac (150mg/day) for more than 4 weeks is contraindicated in
patients with established cardiovascular disease (congestive heart failure, established ischemic
heart disease, peripheral arterial disease) or uncontrolled hypertension. If diclofenac treatment
is needed, patients with established cardiovascular disease, uncontrolled hypertension or
significant cardiovascular risk factors (e.g. hypertension, hyperlipidaemia, diabetes mellitus
Voltfast Sep 2022.SIN Page 3 of 14
and smoking) should be treated only after careful consideration and at doses ≤100 mg daily
when the treatment continues for more than 4 weeks. As the cardiovascular risks of diclofenac
may increase with dose and duration of exposure, diclofenac should always be prescribed
at the lowest effective daily dose and for the shortest duration possible (see section
WARNINGS AND PRECAUTIONS - CARDIOVASCULAR EFFECTS).
Method of administration
Empty contents of one Voltfast
®
sachet into a glass of drinking water. Dissolve well before
drinking. The solution may remain slightly opalescent, but this should not influence the efficacy
of the preparation. The solution should be swallowed preferably before meals. Reconstituted
solution may be stored for up to 24 hours at or below 25ºC.
CONTRAINDICATIONS
•
Known hypersensitivity to the active substance or to any of the excipients.
•
Active gastric or intestinal ulcer, bleeding or perforation (see sections WARNINGS AND
PRECAUTIONS and ADVERSE DRUG REACTIONS).
•
Last trimester of pregnancy (see section PREGNANCY, LACTATION, FEMALES AND
MALES OF REPRODUCTIVE POTENTIAL).
•
Hepatic failure.
•
Renal failure (GFR <15 mL/min/1.73 m
2
).
•
Severe cardiac failure (see section WARNINGS AND PRECAUTIONS).
•
Like other non-steroidal anti-inflammatory drugs (NSAIDs), Voltfast is also contraindicated
in patients in whom the use of acetylsalicylic acid or other NSAIDs can precipitate asthma,
angioedema, urticaria, or acute rhinitis (i.e., NSAID-induced cross-reactivity
reactions)(see sections WARNINGS AND PRECAUTIONS and ADVERSE DRUG
REACTIONS).
•
All NSAIDs should not be used in perioperatively in patients who have recently undergone
coronary artery bypass graft (CABG) surgery and revascularisation procedures.
•
The use of high dose diclofenac (150mg/day) for more than 4 weeks is contraindicated in
patients with established cardiovascular disease (congestive heart failure, established
ischemic heart disease, peripheral arterial disease) or uncontrolled hypertension (see sections
DOSAGE AND ADMINISTRATION - SPECIAL POPULATIONS and WARNINGS
AND PRECAUTIONS - CARDIOVASCULAR EFFECTS).
WARNINGS AND PRECAUTIONS
Gastrointestinal effects
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, have been reported
with all NSAIDs, including diclofenac, and may occur at any time during treatment, with or
without warning symptoms or a previous history of serious gastrointestinal events. They generally
have more serious consequences in the elderly. If gastrointestinal bleeding or ulceration occurs
in patients receiving Voltfast, the treatment should be discontinued.
As with all NSAIDs, including diclofenac, close medical surveillance is imperative and particular
caution should be exercized when prescribing Voltfast in patients with symptoms indicative
of gastrointestinal (GI) disorders or with a history suggestive of gastric or intestinal ulceration,
bleeding or perforation (see section ADVERSE DRUG REACTIONS ). The risk of GI bleeding
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is higher with increasing NSAID doses and in patients with a history of ulcer, particularly if
complicated with hemorrhage or perforation and in the elderly.
To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if complicated
with hemorrhage or perforation, and in the elderly, the treatment should be initiated and
maintained at the lowest effective dose.
Combination therapy with protective agents (e.g., proton pump inhibitors or misoprostol) should
be considered for these patients, and also for patients requiring concomitant use of low-dose
acetylsalicylic acid (ASA) or other drugs likely to increase gastrointestinal risk.
Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal
symptoms (especially GI bleeding). Caution is recommended in patients receiving concomitant
medications which could increase the risk of ulceration or bleeding, such as systemic
corticosteroids, anticoagulants, anti-platelet agents or selective serotonin-reuptake inhibitors (see
section INTERACTIONS).
Close medical surveillance and caution should also be exercised in patients with ulcerative
colitis or Crohn’s disease, as their condition may be exacerbated (see section ADVERSE DRUG
REACTION).
NSAIDs, including diclofenac, may be associated with increased risk of gastro-intestinal
anastomotic leak. Close medical surveillance and caution are recommended when using Voltfast
after gastro-intestinal surgery.
Cardiovascular effects
Treatment with NSAIDs including diclofenac, particularly at high dose and in long term, may
be associated with a small increased risk of serious cardiovascular thrombotic events (including
myocardial infarction and stroke).
As the cardiovascular risks of diclofenac may increase with dose and duration of exposure,
the lowest effective daily dose should be used for the shortest duration possible (see section
DOSAGE AND ADMINISTRATION - SPECIAL POPULATIONS). The patient's need for
symptomatic relief and response to therapy should be re-evaluated periodically, especially
when treatment continues for more than 4 weeks.
Patients should be advised to remain alert for the signs and symptoms of serious
arteriothrombotic events (e.g., chest pain, shortness of breath, weakness, slurring of speech),
which can occur without warnings. Patients should be instructed to see a physician immediately
in case of such an event.
Hematologic effects
Use of Voltfast is recommended only for short-term treatment. If, however, Voltfast is used
for a prolonged period, monitoring of the blood count is recommended, as with other NSAIDs.
Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Patients with
defects of hemostasis should be carefully monitored.
Respiratory effects (pre-existing asthma)
In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e., nasal
polyps), chronic obstructive pulmonary diseases or chronic infections of the respiratory tract
(especially if linked to allergic rhinitis-like symptoms), reactions on NSAIDs like asthma
exacerbations (so-called intolerance to analgesics / analgesics-asthma), Quincke’s edema or
Voltfast Sep 2022.SIN Page 5 of 14
urticaria are more frequent than in other patients. Therefore, special precaution is recommended
in such patients (readiness for emergency). This is applicable as well for patients who are allergic
to other substances, e.g., with skin reactions, pruritus or urticaria.
Hepatobiliary effects
Close medical surveillance is required when prescribing Voltfast to patients with impaired
hepatic function, as their condition may be exacerbated.
As with other NSAIDs, including diclofenac values of one or more liver enzymes may increase.
During prolonged treatment with Voltfast, regular monitoring of hepatic function is indicated
as a precautionary measure. If abnormal liver function tests persist or worsen, if clinical
signs or symptoms consistent with liver disease develop, or if other manifestations occur
(e.g., eosinophilia, rash), Voltfast should be discontinued. Hepatitis may occur with use of
diclofenac without prodromal symptoms.
Caution is called for when using Voltfast in patients with hepatic porphyria, since it may
trigger an attack.
Skin reactions
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson
syndrome and toxic epidermal necrolysis, have been reported very rarely in association with
the use of NSAIDs, including Voltfast (see section ADVERSE DRUG REACTIONS). Patients
appear to be at highest risk of these reactions early in the course of therapy, the onset of the
reaction occurring in the majority of cases within the first month of treatment. Voltfast should
be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of
hypersensitivity.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can
also occur in rare cases with diclofenac without earlier exposure to the drug.
Renal effects
As fluid retention and edema have been reported in association with NSAID therapy, including
diclofenac, particular caution is called for in patients with impaired cardiac or renal function,
history of hypertension, the elderly, patients receiving concomitant treatment with diuretics or
medicinal products that can significantly impact renal function, and in those patients with
substantial extracellular volume depletion from any cause, e.g., before and after major surgery
(see section CONTRAINDICATIONS). Monitoring of renal function is recommended as a
precautionary measure when using Voltfast in such cases. Discontinuation of therapy is normally
followed by a recovery to the pre-treatment state.
Geriatric patients
Caution is indicated in the elderly on basic medical grounds, especially in frail elderly patients
or those with a low body weight.
Interactions with other NSAIDs
The concomitant use of Voltfast with systemic NSAIDs including cyclooxygenase-2 selective
inhibitors, should be avoided due to the potential for additive undesirable effects (see section
INTERACTIONS).
Non-selective NSAIDs may be associated with a small increase in the absolute risk of CVS
events, especially when used at high doses for long-term treatment.
Voltfast Sep 2022.SIN Page 6 of 14
Special excipients
Voltfast contains a source of phenylalanine and may be therefore harmful for patients with
phenylketonuria.
Masking signs of infections
Like other NSAIDs, diclofenac may mask the signs and symptoms of infection due to its
pharmacodynamic properties.
INTERACTIONS
The following interactions include those observed with Voltfast powder for oral solution and/or
other pharmaceutical forms of diclofenac.
Observed interactions to be considered
CYP2C9 inhibitors: Caution is recommended when co-prescribing diclofenac with CYP2C9
inhibitors (such as voriconazole), which could result in a significant increase in peak plasma
concentrations and exposure to diclofenac.
Lithium: If used concomitantly, diclofenac may raise plasma concentrations of lithium.
Monitoring of the serum lithium level is recommended.
Digoxin: If used concomitantly, diclofenac may raise plasma concentrations of digoxin.
Monitoring of the serum digoxin level is recommended.
Diuretics and antihypertensive agents: Like other NSAIDs, concomitant use of diclofenac
with diuretics or antihypertensive agents (e.g., beta-blockers, angiotensin converting enzyme
(ACE) inhibitors) may cause a decrease in their antihypertensive effect. Therefore, the
combination should be administered with caution and patients, especially the elderly, should
have their blood pressure periodically monitored. Patients should be adequately hydrated and
consideration should be given to monitoring of renal function after initiation of concomitant
therapy and periodically thereafter, particularly for diuretics and ACE inhibitors due to the
increased risk of nephrotoxicity (see section WARNINGS AND PRECAUTIONS).
Ciclosporin and tacrolimus: Diclofenac, like other NSAIDs, may increase the nephrotoxicity
of ciclosporin and tacrolimus due to the effect on renal prostaglandins. Therefore, it should be
given at doses lower than those that would be used in patients not receiving ciclosporin or
tacrolimus.
Drugs known to cause hyperkalemia: Concomitant treatment with potassium-sparing diuretics,
ciclosporin, tacrolimus or trimethoprim may be associated with increased serum potassium levels,
which should therefore be monitored frequently (see section WARNINGS AND
PRECAUTIONS).
Quinolone antibacterials: There have been isolated reports of convulsions which may have
been due to concomitant use of quinolones and NSAIDs.
Anticipated interactions to be considered
Other NSAIDs and corticosteroids: Concomitant administration of diclofenac and other
systemic NSAIDs or corticosteroids may increase the frequency of gastrointestinal
undesirable effects (see section WARNINGS AND PRECAUTIONS).
Anticoagulants and anti-platelet agents: Caution is recommended since concomitant
administration could increase the risk of bleeding (see section WARNINGS AND
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PRECAUTIONS). Although clinical investigations do not appear to indicate that diclofenac
affects the action of anticoagulants, there are reports of an increased risk of hemorrhage in
patients receiving diclofenac and anticoagulants concomitantly. Close monitoring of such patients
is therefore recommended.
Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of systemic
NSAIDs, including diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding
(see section WARNINGS AND PRECAUTIONS).
Antidiabetics: Clinical studies have shown that diclofenac can be given together with oral
antidiabetic agents without influencing their clinical effect. However, there have been isolated
reports of both hypoglycaemic and hyperglycaemic effects necessitating changes in the dosage
of the antidiabetic agents during treatment with diclofenac. For this reason, monitoring of
the blood glucose level is recommended as a precautionary measure during concomitant
therapy.
There have also been isolated reports of metabolic acidosis when diclofenac was co-
administered with metformin, especially in patients with pre-existing renal impairment.
Phenytoin: When using phenytoin concomitantly with diclofenac, monitoring of phenytoin
plasma concentrations is recommended due to an expected increase in exposure to phenytoin.
Methotrexate: Caution is recommended when NSAIDs, including diclofenac, are administered
less than 24 hours before or after treatment with methotrexate, since blood concentrations of
methotrexate may rise and the toxicity of this substance be increased.
CYP2C9 inducers: Caution is recommended when co-prescribing diclofenac with CYP2C9
inducers (such as rifampicin), which could result in a significant decrease in plasma
concentration and exposure to diclofenac
PREGNANCY, LACTATION, FEMALES AND MALES OF REPRODUCTIVE
POTENTIAL
Pregnancy
Risk Summary
There are insufficient data on the use of diclofenac in pregnant women. Some epidemiological
studies suggest an increased risk of miscarriage after use of a prostaglandin synthesis
inhibitor (such as NSAIDs) in early pregnancy, however the overall data are inconclusive.
Diclofenac has been shown to cross the placental barrier in humans. Use of NSAIDs, including
diclofenac, can cause uterine inertia, premature closure of the fetal ductus arteriosus and fetal renal
impairment leading to oligohydramnios.
Because of these risks, Volfast is contraindicated in the third trimester of pregnancy (see section
CONTRAINDICATIONS).
Voltfast should not be used during the first two trimesters of pregnancy unless the expected
benefits to the mother outweigh the risks to the fetus. Use of NSAIDs at about 20 weeks gestation
or later in pregnancy may cause foetal renal dysfunction leading to oligohydramnios and, in some
cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to
weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours
after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment
discontinuation.
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Clinical considerations
Fetal Adverse Drug Reactions
Premature Closure of Fetal Ductus Arteriosus
As with other NSAIDs, use of diclofenac during the third trimester of pregnancy is contraindicated
owing to the possibility of premature closure of the fetal ductus arteriosus (see section
CONTRAINDICATIONS).
Oligohydramnios/Fetal Renal Impairment
Risk of fetal renal impairment with subsequent oligohydramnios has been observed when NSAIDs
(including diclofenac) were used from the 20
th
week of pregnancy onwards.
If an NSAID is necessary from the 20th week gestation to the end of the 2nd trimester, limit the use
to the lowest effective dose and shortest duration possible (see section DOSAGE REGIMEN AND
ADMINISTRATION). If Voltfast treatment extends beyond 48 hours, consider monitoring with
ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue Voltfast and follow up
according to clinical practice.
Labor or Delivery
There are no studies on the effects of Voltfast during labor or delivery. As with other NSAIDs, use
of diclofenac during the third trimester of pregnancy is contraindicated owing to the possibility of
uterine inertia (see section CONTRAINDICATIONS). In animal studies, NSAIDS, including
diclofenac, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of
stillbirth.
Data
Human Data
Premature Closure of Fetal Ductus Arteriosus
Published literature reports that the use of NSAIDs during the third trimester of pregnancy may
cause premature closure of the fetal ductus arteriosus.
Oligohydramnios/Fetal Renal Impairment
Published studies and post-marketing reports describe maternal NSAID use at about 20 weeks
gestation or later in pregnancy associated with fetal renal impairment leading to oligohydramnios.
These adverse outcomes are seen, on average, after days to weeks of treatment, although
oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many
cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the
drug.
Animal Data
Reproductive and developmental studies in animals demonstrated that diclofenacadministration
during organogenesis did not produce teratogenicity despite the induction of maternal toxicity and
fetal toxicity in mice at oral doses up to 20 mg/kg/day (0.41 times the maximum recommended
human dose [MRHD] of Voltfast, 200 mg/day, based on body surface area (BSA) comparison), and
in rats and rabbits at oral doses up to 10 mg/kg/day (0.41 and 0.81 times, respectively, the MRHD
based on BSA comparison).
In a study in which pregnant rats were orally administered 2 or 4 mg/kg diclofenac (0.08 and 0.16
times the MRHD based on BSA) from Gestation Day 15 through Lactation Day 21, significant
maternal mortality (caused by gastrointestinal ulceration and peritonitis) was noted. These
maternally toxic doses were associated with dystocia, prolonged gestation, intrauterine growth
retardation, and decreased fetal survival.
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Administration of NSAIDs (including diclofenac) inhibited ovulation in the rabbit and implantation
and placentation in the rat, and led to premature closure of the fetal ductus arteriosus.
Lactation
Risk Summary
Like other NSAIDs, diclofenac passes into the breast milk in small amounts. Therefore, Voltfast
should not be administered during breast feeding in order to avoid undesirable effects in the infant.
Human Data
Diclofenac was detected in a low concentration (100 ng/mL) in breast milk in one nursing mother
treated orally with a diclofenac salt of 150 mg/day. The estimated dose ingested by an infant
consuming breast milk is equivalent to a 0.03 mg/kg/day.
Females and males of reproductive potential
Female fertility
As with other NSAIDs, the use of Voltfast may impair female fertility and is not recommended
in women attempting to conceive. In women who have difficulties conceiving or who are
undergoing investigation of infertility, withdrawal of Voltfast should be considered.
Male fertility
There is no human data on the effect of Voltfast on male fertility.
Diclofenac administered to male and female rats at 4 mg/kg/day (approximately 0.16 times the
MRHD based on BSA comparison) did not affect fertility.
ADVERSE DRUG REACTIONS
Tabulated summary of adverse drug reactions
Adverse drug reactions from clinical trials and/or spontaneous or literature reports (Table 1) are
listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions
are ranked by frequency, with the most frequent reactions first. Within each frequency grouping,
adverse drug reactions are presented in order of decreasing seriousness. In addition, the
corresponding frequency category for each adverse drug reaction is based on the following
convention (CIOMS III): very common (>1/10); common (≥ 1/100 to < 1/10); uncommon (≥
1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000).
The following undesirable effects include those reported with Voltfast powder for oral solution
and/or other pharmaceutical forms of diclofenac, with either short-term or long-term use.
Table 1
Adverse drug reactions
Blood and lymphatic system disorders
Very rare:
Immune system disorders
Rare:
Very rare:
Psychiatric disorders
Very rare:
Nervous system disorders
Common:
Voltfast Sep 2022.SIN Page 10 of 14
Rare:
Very rare:
Eye disorders
Very rare:
Ear and labyrinth disorders
Common:
Very Rare:
Cardiac disorders
Uncommon*:
Frequency not known:
Vascular disorders
Very rare:
Respiratory, thoracic and mediastinal disorders
Rare:
Very rare:
Gastrointestinal disorders
Common:
Rare:
Very rare:
Hepatobiliary disorders
Common
Rare:
Very rare:
Skin and subcutaneous tissue disorders
Common
Rare:
Very rare:
Renal and urinary disorders
Very rare:
General disorders and administration site conditions
Rare:
* The frequency reflects data from long-term treatment with a high dose (150 mg daily)
Description of selected adverse drug reactions
Arteriothrombotic events
Meta-analysis and pharmacoepidemiological data point towards a small increased risk of
arteriothrombotic events (for example myocardial infarction) associated with the use of
diclofenac, particularly at a high dose (150 mg daily) and during long-term treatment (see
section WARNINGS AND PRECAUTIONS).
Visual effects
Visual disturbances such as visual impairment, blurred vision or diplopia appear to be NSAID
class effects and are usually reversible on discontinuation. A likely mechanism for the visual
disturbances is the inhibition of prostaglandin synthesis and other related compounds that
Voltfast Sep 2022.SIN Page 11 of 14
alter the regulation of retinal blood flow resulting in potential changes in vision. If such
symptoms occur during diclofenac treatment, an ophthalmological examination may be
considered to exclude other causes
OVERDOSAGE
Symptoms
There is no typical clinical picture resulting from diclofenac overdosage. Overdosage can
cause symptoms such as vomiting, gastrointestinal hemorrhage, diarrhea, dizziness, tinnitus or
convulsions. In the event of significant poisoning, acute renal failure and liver damage are
possible.
Therapeutic measures
Management of acute poisoning with NSAIDs, including diclofenac, essentially consists of
supportive measures and symptomatic treatment. Supportive measures and symptomatic
treatment should be given for complications such as hypotension, renal failure, convulsions,
gastrointestinal disorder, and respiratory depression.
Special measures such as forced diuresis, dialysis or hemoperfusion are probably of no help
in eliminating NSAIDs, including diclofenac, due to the high protein-binding and extensive
metabolism.
Activated charcoal may be considered after ingestion of a potentially toxic overdose, and
gastric decontamination (e.g., vomiting, gastric lavage) after ingestion of a potentially life-
threatening overdose.
CLINICAL PHARMACOLOGY
Pharmacotherapeutic group, ATC
Anti-inflammatory and antirheumatic products, non-steroids, acetic acid derivatives and related
substances (ATC code: M01A B05).
Mechanism of action (MOA)
Voltfast contains diclofenac potassium, a non-steroidal compound with pronounced
antirheumatic, analgesic, anti-inflammatory, and antipyretic properties.
Voltfast has a rapid onset of action, which makes it particularly suitable for the treatment of
acute painful and inflammatory conditions. Inhibition of prostaglandin biosynthesis, which
has been demonstrated in experiments, is considered to be fundamental to its mechanism of
action. Prostaglandins play a major role in causing inflammation, pain, and fever.
Diclofenac potassium in vitro does not suppress proteoglycan biosynthesis in cartilage at
concentrations equivalent to the concentrations reached in humans.
Pharmacodynamics (PD)
Voltfast has been found to exert a pronounced analgesic effect in moderate and severe pain.
In the presence of inflammation, e.g., due to trauma or following surgical interventions, it
rapidly relieves both spontaneous pain and pain on movement and diminishes inflammatory
swelling and wound edema. Clinical studies have also revealed that in primary dysmenorrhoea
the active substance is capable of relieving the pain and reducing the extent of bleeding. In
migraine attacks Voltfast has been shown to be effective in relieving the headache and in
improving the accompanying symptoms nausea and vomiting.
Voltfast Sep 2022.SIN Page 12 of 14
Pharmacokinetics (PK)
Absorption
Diclofenac is rapidly and completely absorbed from diclofenac potassium. Mean peak plasma
concentrations of 5.5 micromol/L are attained after 5 to 20 minutes after ingestion of one
sachet of 50 mg.
Ingestion together with food is expected to have no influence on the amount of diclofenac
absorbed although onset and rate of absorption may be slightly delayed.
Since about half of diclofenac is metabolized during its first passage through the liver ("first
pass" effect), the area under the concentration curve (AUC) is about half as large following
oral or rectal administration as it is following a parenteral dose of equal size.
Pharmacokinetic behaviour does not change after repeated administration. No accumulation
occurs provided the recommended dosage intervals are observed.
Distribution
99.7% of diclofenac binds to serum proteins, mainly to albumin (99.4%). The apparent volume
of distribution calculated is 0.12 to 0.17 L/kg.
Diclofenac enters the synovial fluid, where maximum concentrations are measured 2 to 4
hours after peak plasma values have been reached. The apparent half-life for elimination from
the synovial fluid is 3 to 6 hours. Two hours after reaching peak plasma levels, concentrations
of the active substance are already higher in the synovial fluid than in the plasma, and they
remain higher for up to 12 hours.
Biotransformation/metabolism
Biotransformation of diclofenac takes place partly by glucuronidation of the intact molecule,
but mainly by single and multiple hydroxylation and methoxylation, resulting in several phenolic
metabolites (3'-hydroxy-, 4'-hydroxy-, 5-hydroxy-, 4',5-dihydroxy-, and 3'-hydroxy- 4'-
methoxy-diclofenac), most of which are converted to glucuronide conjugates. Two of these
phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.
Elimination
Total systemic clearance of diclofenac from plasma is 263 ± 56 mL/min (mean value ± SD).
The terminal half-life in plasma is 1 to 2 hours. Four of the metabolites, including the two
active ones, also have short plasma half-lives of 1 to 3 hours. One metabolite, 3’-hydroxy-4’-
methoxy-diclofenac, has a much longer plasma half-life. However, this metabolite is virtually
inactive.
About 60% of the administered dose is excreted in the urine as the glucuronide conjugate of
the intact molecule and as metabolites, most of which are also converted to glucuronide
conjugates. Less than 1% is excreted as unchanged substance. The rest of the dose is eliminated
as metabolites through the bile in the faeces.
Linearity/non-linearity
The amount absorbed is in linear proportion to the size of the dose.
Voltfast Sep 2022.SIN Page 13 of 14
Special populations
Geriatric patients
No relevant age-dependent differences in the drug’s absorption, metabolism or excretion have
been observed.
Renal impairment
In patients suffering from renal impairment, no accumulation of the unchanged active substance
can be inferred from the single-dose kinetics when applying the usual dosage schedule. At a
creatinine clearance of less than 10 mL/min, the calculated steady-state plasma levels of the
hydroxy metabolites are about 4 times higher than in normal subjects. However, the metabolites
are ultimately cleared through the bile.
Hepatic impairment
In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics and metabolism
of diclofenac are the same as in patients without liver disease.
NON-CLINICAL SAFETY DATA
Preclinical data from acute and repeated dose toxicity studies, as well as from genotoxicity,
mutagenicity, and carcinogenicity studies with diclofenac revealed no specific hazard for
humans at the intended therapeutic doses.
For more information, see section PREGNANCY, LACTATION, FEMALES AND MALES OF
REPRODUCTIVE POTENTIAL
PHARMACEUTICAL INFORMATION
Incompatibilities
Not applicable.
Storage
See folding box.
Store at or below 30°C.
Store in the original package in order to protect from moisture.
Voltfast powder for oral solution should not be used after the date marked “EXP” on the pack.
Voltfast powder for oral solution must be kept out of the reach and sight of children.
Instructions for use and handling
No special requirements.
Manufacturer:
See folding box.
Package Leaflet
= registered trademark
Voltfast Sep 2022.SIN Page 14 of 14
Novartis Pharma AG, Basel, Switzerland