DPWG

Dutch Pharmacogenetics Working Group

National expert working group

4 drugs 4 brand products

About DPWG

The Dutch Pharmacogenetics Working Group (DPWG) was established by the Royal Dutch Pharmacists Association (KNMP) to develop pharmacogenetic prescribing advice for use in the Netherlands. Like CPIC, the DPWG reviews the evidence for a gene-drug pair and issues specific dosing recommendations for each phenotype, which are distributed internationally through PharmGKB.^[1] The two bodies work independently and occasionally reach different conclusions, so a DPWG recommendation is a useful second expert opinion alongside CPIC.

What guidance it offers

Gene2Rx includes a curated set of DPWG recommendations where they add clinically meaningful guidance beyond CPIC and the FDA, currently covering haloperidol, quetiapine, allopurinol, and zuclopenthixol. For each of these drugs the DPWG provides phenotype-specific advice, such as a dose adjustment or a switch to an alternative, shown in the table below.

Visit the DPWG source →

Drugs with DPWG guidance

Gene2Rx reports DPWG pharmacogenetic guidance for 4 drugs, grouped by therapeutic class. Expand any drug to see the DPWG recommendation for each metabolizer group, or open its full pharmacogenetics page.

antipsychotics →

Haloperidol CYP2D6

Metabolizer group	What it means	DPWG recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased CYP2D6 activity leads to accelerated conversion of haloperidol. Plasma concentration is approximately 40% lower than in Normal Metabolizers, risking reduced effectiveness.	Use 1.5 times the normal dose, or choose an alternative. Antipsychotics not metabolised (or metabolised to a much lesser extent) by CYP2D6 include flupentixol, penfluridol, quetiapine, olanzapine, or clozapine.	Moderate
Normal Metabolizer CYP2D6	No clinically significant effect on haloperidol metabolism.	Use standard haloperidol dosing.	Moderate
Intermediate Metabolizer CYP2D6	Slightly reduced CYP2D6 activity produces a modest increase in haloperidol plasma concentration, but the effect is small and no clinically significant consequences have been observed.	No action is required. Use standard haloperidol dosing.	Moderate
Poor Metabolizer CYP2D6	Decreased CYP2D6 activity reduces conversion of haloperidol, increasing plasma concentration approximately 1.7-fold. This is associated with an increased risk of side effects.	Use 60% of the normal dose.	Moderate

Quetiapine CYP3A4

Metabolizer group	What it means	DPWG recommendation	Evidence
Normal Metabolizer CYP3A4	No clinically significant effect on quetiapine metabolism.	Use standard quetiapine dosing.	Moderate
Intermediate Metabolizer CYP3A4	Slightly reduced CYP3A4 activity yields approximately a 20% increase in quetiapine plasma concentration. The clinical significance is limited and the plasma concentration–clinical effect relationship for quetiapine is weak.	No action is required. Use standard quetiapine dosing.	Moderate
Poor Metabolizer CYP3A4	Markedly reduced CYP3A4 activity increases quetiapine plasma concentration approximately 3.2-fold and reduces formation of the active antidepressant metabolite N-desalkylquetiapine. Risk of adverse effects is elevated and antidepressant efficacy may be reduced.	Depression indication: choose an alternative agent (aripiprazole is less dependent on CYP3A4; olanzapine is not metabolised by CYP3A4). Other indications: use 30% of the normal quetiapine dose.	Moderate

Zuclopenthixol CYP2D6

Metabolizer group	What it means	DPWG recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased CYP2D6 activity accelerates zuclopenthixol conversion, which can reduce plasma concentration and risk ineffectiveness.	Insufficient data to make a firm dosage recommendation. If effectiveness is insufficient, try a dose increase — do not exceed 1.5 times the normal dose. Alternatively, consider an antipsychotic that is not metabolised (or to a lesser extent) by CYP2D6 (e.g., flupentixol, quetiapine, olanzapine, clozapine).	Moderate
Normal Metabolizer CYP2D6	No clinically significant effect on zuclopenthixol metabolism.	Use standard zuclopenthixol dosing.	Moderate
Intermediate Metabolizer CYP2D6	Decreased CYP2D6 activity reduces conversion of zuclopenthixol, raising plasma concentration approximately 1.35-fold. This may increase the risk of side effects.	Use 75% of the normal dose.	Moderate
Poor Metabolizer CYP2D6	Markedly decreased CYP2D6 activity reduces conversion of zuclopenthixol, raising plasma concentration approximately 1.6-fold and elevating side effect risk.	Use 50% of the normal dose.	Moderate

gout →

Allopurinol ABCG2

Metabolizer group	What it means	DPWG recommendation	Evidence
Normal Function ABCG2	Normal ABCG2 transporter function. Renal and intestinal uric acid excretion is not impaired by ABCG2 variation at p.Gln141Lys.	Use standard allopurinol dosing.	Moderate
Decreased Function ABCG2	One copy of the p.Gln141Lys (rs2231142 G>T) variant reduces ABCG2 transporter function, which reduces renal and intestinal excretion of uric acid. As a result, a higher allopurinol dose is needed to suppress uric acid production to the target concentration.	Use 1.25 times the standard allopurinol dose. Equivalent titration schedule: 100, 200, 400, 500 mg/day instead of the usual 100, 200, 300, 400 mg/day.	Moderate
Poor Function ABCG2	Two copies of the p.Gln141Lys (rs2231142 G>T) variant substantially reduce ABCG2 transporter function. Renal and intestinal uric acid excretion is impaired, and a higher allopurinol dose is needed for uric acid suppression.	Use 1.4 times the standard allopurinol dose. Equivalent titration schedule: 100, 300, 400, 600, 700 mg/day instead of the usual 100, 200, 300, 400, 500 mg/day.	Moderate

Brand products with DPWG-guided ingredients

These branded medications contain at least one active ingredient with DPWG pharmacogenetic guidance. Each links to its full breakdown.

References

DPWG / KNMP, via PharmGKB. Dutch Pharmacogenetics Working Group (DPWG) Guidelines. pharmgkb.org
PharmGKB / Stanford University. PharmGKB: The Pharmacogenomics Knowledge Base. pharmgkb.org

See your own DPWG guidance

This page lists the drugs DPWG covers. A Gene2Rx report tells you which metabolizer group you fall into, and what that means for each of these medications.

Get your report All guidance sources

Informational only, not medical advice. The presence of a DPWG pharmacogenetic guideline does not mean every patient needs to change their dose. Never start, stop, or change a medication without talking to your prescribing clinician.