Consumer medicine information

1. Why am I taking DOVATO?

DOVATO contains the active ingredients dolutegravir and lamivudine. DOVATO is used to treat HIV infection.
For more information, see Section 1. Why am I taking DOVATO? in the full CMI.

2. What should I know before I take DOVATO?

Do not use if you have ever had an allergic reaction to dolutegravir, lamivudine or any of the ingredients listed at the end of the CMI.
Do not take DOVATO if you are taking dofetilide or pilsicainide (used to treat heart conditions) or fampridine (for multiple sclerosis).
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I take DOVATO? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DOVATO and affect how it works.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take DOVATO?

• The usual dosage of DOVATO is one tablet once a day

• Swallow the tablet whole with a glass of water

5. What should I know while taking DOVATO?

6. Are there any side effects?

Side effects that have been reported include headache, feeling sick (nausea) and vomiting, abdominal pain or discomfort, diarrhoea, increased wind (flatulence), fatigue, tiredness, lack of energy, a general feeling of being unwell, fever, dizziness, loss of hair, rash and itching, joint pain, muscle pain, weight gain, abnormal dreams, difficulty sleeping, depression, anxiety, having suicidal thoughts (mainly in patients who have had depression or mental health problems previously).
Allergic reaction has also been reported. Signs include swelling of the lips, tongue, wheezing or difficulty breathing, rash, hives on the skin. If this occurs seek medical attention immediately.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Dolutegravir (as dolutegravir sodium) and lamivudine.

2 Qualitative and Quantitative Composition

Dovato film-coated tablets contain 50 mg of dolutegravir (as dolutegravir sodium) and 300 mg of lamivudine. Product information for dolutegravir and lamivudine contain additional information.
Dolutegravir sodium is a white to light yellow powder.
Lamivudine is a white to off-white crystalline solid.
Dovato tablets also contain mannitol.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Oval, biconvex, white, film-coated tablet, debossed with "SV 137" on one face.

4 Clinical Particulars

4.9 Overdose

Symptoms and signs. There is currently limited experience with over-dosage in dolutegravir. Limited experience of single higher doses (up to 250 mg in healthy subjects) revealed no specific symptoms or signs, apart from those listed as adverse reactions.
No specific symptoms or signs have been identified following acute overdose with lamivudine, apart from those listed as adverse reactions.
Treatment. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary. Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdose, although this has not been studied. As dolutegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. No genotoxicity studies have been conducted with the combination of dolutegravir and lamivudine.
Dolutegravir was not mutagenic or clastogenic using in vitro tests in bacteria and cultured mammalian cells, and an in vivo rodent micronucleus assay.
Lamivudine was not mutagenic in bacterial tests, but induced mutations in a mouse lymphoma assay and was clastogenic in human peripheral lymphocytes in vitro. In rats, lamivudine did not cause chromosomal damage in bone marrow cells in vivo or cause DNA damage in primary hepatocytes.
Carcinogenicity. No carcinogenicity studies have been conducted with the combination of dolutegravir and lamivudine.
In long-term oral carcinogenicity studies conducted with dolutegravir no drug-related increases in tumour incidence were found in mice at doses up to 500 mg/kg/day (20 times the human systemic exposure based on AUC at the maximum recommended dose of 50 mg QD) or in rats at doses up to 50 mg/kg/day (17 times the human systemic exposure based on AUC at the maximum recommended dose).
When lamivudine was administered orally in the diet to separate groups of rodents at doses up to 2,000 (mice and male rats) and 3,000 (female rats) mg/kg/day, there was no evidence of a carcinogenic effect due to lamivudine in the mouse study. In the rat study there was an increased incidence of endometrial tumours at the highest dose (approximately 70 times the estimated human exposure at the recommended therapeutic dose of 300 mg daily, based on AUC). However, the relationship of this increase to treatment is uncertain.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Dolutegravir. The chemical (IUPAC) name for dolutegravir sodium is Sodium (4R,12aS)-9-{[(2,4-difluorophenyl)methyl] carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5] pyrazino[2,1-b][1,3]oxazin-7-olate.
Molecular formula: C₂₀H₁₈F₂N₃NaO₅.
Molecular weight of 441.36 g/mol.
The partition coefficient (log P) for dolutegravir sodium is 2.2 and the pKa is 8.2.
Dolutegravir sodium is slightly soluble in water.
Lamivudine. The chemical name of lamivudine is (2R,cis)-4-amino-1-[2-(hydroxymethyl)- 1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone. Lamivudine is the (-)enantiomer of a dideoxy analogue of cytidine. Lamivudine has also been referred to as (-)2',3'-dideoxy,3'-thiacytidine.
Molecular formula: C₈H₁₁N₃O₃S.
Molecular weight of 229.3 g/mol.
Lamivudine is highly soluble in water.
Chemical structure. The structural formula of dolutegravir sodium is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSDOLUTE.gif The structural formula of lamivudine is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSLAMIVU.gif CAS number. 1051375-19-9 (dolutegravir sodium); 134678-17-4 (lamivudine).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/DOVATOST.gif